Neurodegenerative disease

615: 540:, vision loss, and shortened lifespan. A loss of vision is common first sign of Batten disease. Loss of vision is typically preceded by cognitive and behavioral changes, seizures, and loss of the ability to walk. It is common for people to establish cardiac arrhythmias and difficulties eating food as the disease progresses. Batten disease diagnosis depends on a conflation of many criteria: clinical signs and symptoms, evaluations of the eye, electroencephalograms (EEG), and brain magnetic resonance imaging (MRI) results. The diagnosis provided by these results are corroborated by genetic and biochemical testing. No effective treatments were available to prevent the disease from being widespread before the past few years. In recent years, more models have been created to expedite the research process for methods to treat Batten disease. 492:) is thought to be the most common known cause of sporadic ALS. Early diagnosis of ALS is harder than with other neurodegenerative diseases as there are no highly effective means of determining its early onset. Currently, there is research being done regarding the diagnosis of ALS through upper motor neuron tests. The Penn Upper Motor Neuron Score (PUMNS) consists of 28 criteria with a score range of 0–32. A higher score indicates a higher level of burden present on the upper motor neurons. The PUMNS has proven quite effective in determining the burden that exists on upper motor neurons in affected patients. 208:. It is the most common neurodegenerative disease. Even with billions of dollars being used to find a treatment for Alzheimer's disease, no effective treatments have been found. Within clinical trials stable and effective AD therapeutic strategies have a 99.5% failure rate. Reasons for this failure rate include inappropriate drug doses, invalid target and participant selection, and inadequate knowledge of pathophysiology of AD. Currently, diagnoses of Alzheimer's is subpar, and better methods need to be utilized for various aspects of clinical diagnoses. Alzheimer's has a 20% misdiagnosis rate. 39: 443:

experience early relapsing and remitting episodes of neuronal deterioration following a period of recovery. Some of these individuals may transition to a more linear progression of the disease, while about 15% of others begin with a progressive course on the onset of multiple sclerosis. The inflammatory response contributes to the loss of the grey matter, and as a result current literature devotes itself to combatting the auto-inflammatory aspect of the disease. While there are several proposed causal links between EBV and the

124:. Neurodegeneration can be found in the brain at many different levels of neuronal circuitry, ranging from molecular to systemic.Because there is no known way to reverse the progressive degeneration of neurons, these diseases are considered to be incurable; however research has shown that the two major contributing factors to neurodegeneration are oxidative stress and inflammation. Biomedical research has revealed many similarities between these diseases at the 6874: 160: 426:, caused by an autoimmune attack resulting in the progressive loss of myelin sheath on neuronal axons. The resultant decrease in the speed of signal transduction leads to a loss of functionality that includes both cognitive and motor impairment depending on the location of the lesion. The progression of MS occurs due to episodes of increasing inflammation, which is proposed to be due to the release of antigens such as 6886: 303:, may play a role in this disease mechanism. Impaired axonal transport of alpha-synuclein may also lead to its accumulation in Lewy bodies. Experiments have revealed reduced transport rates of both wild-type and two familial Parkinson's disease-associated mutant alpha-synucleins through axons of cultured neurons. Membrane damage by alpha-synuclein could be another Parkinson's disease mechanism. 6432: 318:(MAPT) can also cause hereditary PD or increase PD risk. While PD is the second most common neurodegenerative disorder, problems with diagnoses still persist. Problems with the sense of smell is a widespread symptom of Parkinson's disease (PD), however, some neurologists question its efficacy. This assessment method is a source of controversy among medical professionals. The 532:(NCLs) – each caused by a specific gene mutation, of which there are thirteen. Since Batten disease is quite rare, its worldwide prevalence is about 1 in every 100,000 live births. In North America, NCL3 disease (juvenile NCL) typically manifests between the ages of 4 and 7. Batten disease is characterized by motor impairment, 1430:

by Medivation, Inc. In 2009 this drug was in phase III clinical trials for use in Alzheimer's disease, and also phase II clinical trials for use in Huntington's disease. In March 2010, the results of a clinical trial phase III were released; the investigational Alzheimer's disease drug Dimebon failed

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along with enzymes is key for the degradation of many proteins that cause proteopathies including polyQ expansions and alpha-synucleins. Research indicates proteasome enzymes may not be able to correctly cleave these irregular proteins, which could possibly result in a more toxic species. This is the

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A current therapeutic target for the treatment of Alzheimer's disease is the protease β-secretase, which is involved in the amyloidogenic processing pathway that leads to the pathological accumulation of proteins in the brain. When the gene that encodes for amyloid precursor protein (APP) is spliced

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Polyglutamine repeats typically cause dominant pathogenesis. Extra glutamine residues can acquire toxic properties through a variety of ways, including irregular protein folding and degradation pathways, altered subcellular localization, and abnormal interactions with other cellular proteins. PolyQ

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Protein degradation offers therapeutic options both in preventing the synthesis and degradation of irregular proteins. There is also interest in upregulating autophagy to help clear protein aggregates implicated in neurodegeneration. Both of these options involve very complex pathways that we are

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is involved with nutrient recycling of macromolecules under conditions of starvation, certain apoptotic pathways, and if absent, leads to the formation of ubiquinated inclusions. Experiments in mice with neuronally confined macroautophagy-gene knockouts develop intraneuronal aggregates leading to

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accumulation provides the underlying causative link between aging and neurodegenerative disease. About 20–40% of healthy people between 60 and 78 years old experience discernable decrements in cognitive performance in several domains including working, spatial, and episodic memory, and processing

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of disease to test potential therapeutic agents. Model organisms provide an inexpensive and relatively quick means to perform two main functions: target identification and target validation. Together, these help show the value of any specific therapeutic strategies and drugs when attempting to

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is particularly harmful because DNA is the blueprint for protein production and unlike other molecules it cannot simply be replaced by re-synthesis. The vulnerability of post-mitotic neurons to DNA damage (such as oxidative lesions or certain types of DNA strand breaks), coupled with a gradual

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to cross the blood-brain barrier and attack myelin on neuronal axons leading to inflammation. Further release of antigens drives subsequent degeneration causing increased inflammation. Multiple sclerosis presents itself as a spectrum based on the degree of inflammation, a majority of patients

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in any form, mediated by an intracellular program. This process can be activated in neurodegenerative diseases including Parkinson's disease, amytrophic lateral sclerosis, Alzheimer's disease and Huntington's disease. PCD observed in neurodegenerative diseases may be directly pathogenic;

382:. Huntington's disease presents itself later in life even though the proteins that cause the disease works towards manifestation from their early stages in the humans affected by the proteins. Along with being a neurodegenerative disorder, HD has links to problems with neurodevelopment. 926:

Damage to the membranes of organelles by monomeric or oligomeric proteins could also contribute to these diseases. Alpha-synuclein can damage membranes by inducing membrane curvature, and cause extensive tubulation and vesiculation when incubated with artificial phospholipid vesicles.

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both contribute to aging. Many of these diseases are late-onset, meaning there is some factor that changes as a person ages for each disease. One constant factor is that in each disease, neurons gradually lose function as the disease progresses with age. It has been proposed that

272:, rigidity, resting tremor and posture instability. The crude prevalence rate of PD has been reported to range from 15 per 100,000 to 12,500 per 100,000, and the incidence of PD from 15 per 100,000 to 328 per 100,000, with the disease being less common in Asian countries. 1431:

in the pivotal CONNECTION trial of patients with mild-to-moderate disease. With CONCERT, the remaining Pfizer and Medivation Phase III trial for Dimebon (latrepirdine) in Alzheimer's disease failed in 2012, effectively ending the development in this indication.

476:(LMNs). Although initial symptoms may vary, most patients develop skeletal muscle weakness that progresses to involve the entire body. The precise etiology of ALS remains unknown. In 1993, missense mutations in the gene encoding the antioxidant enzyme 1210:

PCD can also occur via non-apoptotic processes, also known as Type III or cytoplasmic cell death. For example, type III PCD might be caused by trophotoxicity, or hyperactivation of trophic factor receptors. Cytotoxins that induce PCD can cause

1202:, which fuses with a lysosome to destroy the contents of the autophagosome. Because many neurodegenerative diseases show unusual protein aggregates, it is hypothesized that defects in autophagy could be a common mechanism of neurodegeneration. 1434:

In another experiment using a rat model of Alzheimer's disease, it was demonstrated that systemic administration of hypothalamic proline-rich peptide (PRP)-1 offers neuroprotective effects and can prevent neurodegeneration in hippocampus

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have been observed in many different neurodegenerative diseases. This suggests that defective axons are not only present in diseased neurons, but also that they may cause certain pathological insult due to accumulation of organelles.

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at low concentrations, or aponecrosis (combination of apoptosis and necrosis) at higher concentrations. It is still unclear exactly what combination of apoptosis, non-apoptosis, and necrosis causes different kinds of aponecrosis.

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by α-secretase rather than β-secretase, the toxic protein β amyloid is not produced. Targeted inhibition of β-secretase can potentially prevent the neuronal death that is responsible for the symptoms of Alzheimer's disease.

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Galoyan AA, Sarkissian JS, Chavushyan VA, Meliksetyan IB, Avagyan ZE, Poghosyan MV, et al. (September 2008). "Neuroprotection by hypothalamic peptide proline-rich peptide-1 in Abeta25-35 model of Alzheimer's disease".

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is to enhance aspects of the immune system. Both active and passive vaccinations have been proposed for Alzheimer's disease and other conditions; however, more research must be done to prove safety and efficacy in humans.

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Hill-Burns, Erin M.; Debelius, Justine W.; Morton, James T.; Wissemann, William T.; Lewis, Matthew R.; Wallen, Zachary D.; Peddada, Shyamal D.; Factor, Stewart A.; Molho, Eric; Zabetian, Cyrus P.; Knight, Rob (May 2017).

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is a form of programmed cell death in multicellular organisms. It is one of the main types of programmed cell death (PCD) and involves a series of biochemical events leading to a characteristic cell morphology and death.

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defects may also lead to neurodegeneration. Research has shown that mutant proteins bind to the CMA-pathway receptors on lysosomal membrane and in doing so block their own degradation as well as the degradation of other

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Nabais, Marta F.; Laws, Simon M.; Lin, Tian; Vallerga, Costanza L.; Armstrong, Nicola J.; Blair, Ian P.; Kwok, John B.; Mather, Karen A.; Mellick, George D.; Sachdev, Perminder S.; Wallace, Leanne (2021-03-26).

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Levine, Kristin S.; Leonard, Hampton L.; Blauwendraat, Cornelis; Iwaki, Hirotaka; Johnson, Nicholas; Bandres-Ciga, Sara; Ferrucci, Luigi; Faghri, Faraz; Singleton, Andrew B.; Nalls, Mike A. (19 January 2023).

378:, which initiates and modulates motion. The weaker signals from subthalamic nuclei thus cause reduced initiation and modulation of movement, resulting in the characteristic movements of the disorder, notably 929:

The tubes formed from these lipid vesicles consist of both micellar as well as bilayer tubes. Extensive induction of membrane curvature is deleterious to the cell and would eventually lead to cell death.

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Barnat, Monia; Capizzi, Mariacristina; Aparicio, Esther; Boluda, Susana; Wennagel, Doris; Kacher, Radhia; Kassem, Rayane; Lenoir, Sophie; Agasse, Fabienne; Braz, Barbara Y.; Liu, Jeh-Ping (2020-08-14).

1039:, could lead to accumulation of DNA damage with age and contribute to brain aging and neurodegeneration. DNA single-strand breaks are common and are associated with the neurodegenerative disease ataxia- 657:, most of which are located in completely unrelated genes. In many of the different diseases, the mutated gene has a common feature: a repeat of the CAG nucleotide triplet. CAG codes for the amino acid 879:

Decreased proteasome activity is consistent with models in which intracellular protein aggregates form. It is still unknown whether or not these aggregates are a cause or a result of neurodegeneration.

961:) is a central feature of all neurodegenerative disorders. In addition to the generation of ROS, mitochondria are also involved with life-sustaining functions including calcium homeostasis, PCD, 839:

Parkinson's disease and Huntington's disease are both late-onset and associated with the accumulation of intracellular toxic proteins. Diseases caused by the aggregation of proteins are known as

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The most common form of cell death in neurodegeneration is through the intrinsic mitochondrial apoptotic pathway. This pathway controls the activation of caspase-9 by regulating the release of

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There is strong evidence that mitochondrial dysfunction and oxidative stress play a causal role in neurodegenerative disease pathogenesis, including in four of the more well known diseases

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Svob Strac, Dubravka; Konjevod, Marcela; Sagud, Marina; Nikolac Perkovic, Matea; Nedic Erjavec, Gordana; Vuic, Barbara; Simic, Goran; Vukic, Vana; Mimica, Ninoslav; Pivac, Nela (2021).

4573:"Chronic oxidative damage together with genome repair deficiency in the neurons is a double whammy for neurodegeneration: Is damage response signaling a potential therapeutic target?" 953:(ROS) are normal byproducts of mitochondrial respiratory chain activity. ROS concentration is mediated by mitochondrial antioxidants such as manganese superoxide dismutase (SOD2) and 5787: 5152:

Esch FS, Keim PS, Beattie EC, Blacher RW, Culwell AR, Oltersdorf T, et al. (June 1990). "Cleavage of amyloid beta peptide during constitutive processing of its precursor".

507:. The specific mechanism of toxicity still needs to be investigated, but the findings are significant because they implicate cells other than neuron cells in neurodegeneration. 6173: 6168: 764:. Alpha-synuclein is the primary structural component of Lewy body fibrils. In addition, an alpha-synuclein fragment, known as the non-Abeta component (NAC), is found in 6185: 6163: 4935:

Caccamo D, Currò M, Condello S, Ferlazzo N, Ientile R (February 2010). "Critical role of transglutaminase and other stress proteins during neurodegenerative processes".

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The consequences of neurodegeneration can vary widely depending on the specific region affected, ranging from issues related to movement to the development of dementia.

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Quinn C, Edmundson C, Dahodwala N, Elman L (April 2020). "Reliable and efficient scale to assess upper motor neuron disease burden in amyotrophic lateral sclerosis".

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Turner PR, O'Connor K, Tate WP, Abraham WC (May 2003). "Roles of amyloid precursor protein and its fragments in regulating neural activity, plasticity and memory".

1186:. Initiator caspases cleave inactive forms of effector caspases. This activates the effectors that in turn cleave other proteins resulting in apoptotic initiation. 891:(PCD), this becomes the favorable route when a protein is aggregate-prone meaning it is a poor proteasome substrate. This can be split into two forms of autophagy: 5336: 5109:

Pastorino L, Ikin AF, Lamprianou S, Vacaresse N, Revelli JP, Platt K, et al. (April 2004). "BACE (beta-secretase) modulates the processing of APLP2 in vivo".

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studies often use a variety of animal models because there is such a clearly defined trigger – repeat expansion. Extensive research has been done using the

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allele to the onset of MS – they may contribute to the degree of autoimmune attack and the resultant inflammation – they do not determine the onset of MS.

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of these proteins and peptides make them clump together. The resulting structures are turned extremely resistant to chemical and mechanical disruption.

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disease that is characterized by rapidly progressive dementia. Misfolded proteins called prions aggregate in brain tissue leading to nerve cell death.

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Tiraboschi P, Hansen LA, Thal LJ, Corey-Bloom J (June 2004). "The importance of neuritic plaques and tangles to the development and evolution of AD".

5532: 3735: 1624: 5527: 1494: 2740:"Parkinson's disease and Parkinson's disease medications have distinct signatures of the gut microbiome: PD, Medications, and Gut Microbiome" 6794: 5329: 614: 235:

that penetrates through the neuron's membrane. APP appears to play roles in normal neuron growth, survival and post-injury repair. APP is

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Estrada Sánchez AM, Mejía-Toiber J, Massieu L (April 2008). "Excitotoxic neuronal death and the pathogenesis of Huntington's disease".

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Hooper NM (April 2005). "Roles of proteolysis and lipid rafts in the processing of the amyloid precursor protein and prion protein".

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It has been proved that in these neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, and Huntington's disease) the

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endoplasmic reticulum (ER), (as seen with neuroserpin mutations that cause familial encephalopathy with neuroserpin inclusion bodies)

648: 251:. One of these fragments gives rise to fibrils of amyloid beta which can self-assemble into the dense extracellular amyloid plaques. 3595:

Johnson, Tyler B.; Cain, Jacob T.; White, Katherine A.; Ramirez-Montealegre, Denia; Pearce, David A.; Weimer, Jill M. (March 2019).

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is a rare and fatal recessive neurodegenerative disorder that begins in childhood. Batten disease is the common name for a group of

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might play a role in the diagnosis of PD, and research suggests various ways that could revolutionize the future of PD treatment.

6145: 5322: 1651:"Whole-Brain Dynamics Disruptions in the Progression of Alzheimer's Disease: Understanding the Influence of Amyloid-Beta and Tau" 822: 4086: 1696:"The Emerging Scenario of the Gut-Brain Axis: The Therapeutic Actions of the New Actor Kefir against Neurodegenerative Diseases" 393:

in neurons, and may be directly toxic. Additionally, they may damage molecular motors and microtubules to interfere with normal

6266: 6125: 5798: 1575:"A Review of the Common Neurodegenerative Disorders: Current Therapeutic Approaches and the Potential Role of Nanotherapeutics" 1044: 6150: 5782: 3875: 3112: 2802: 2142: 2054: 2022: 562: 163:

Comparison of brain tissue between healthy individual and Alzheimer's disease patient, demonstrating extent of neuronal death

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The presence of epigenetic modifications for certain genes has been demonstrated in this type of pathology. An example is

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Nine inherited neurodegenerative diseases are caused by the expansion of the CAG trinucleotide and polyQ tract, including

630:) viral exposures can significantly elevate risks of neurodegenerative disease, including up to 15 years after infection. 427: 593: 6207: 6140: 5695: 1145:

Occur when factors outside the cell activate cell surface death receptors (e.g., Fas) that result in the activation of

438:, causing an autoimmune response. This sets off a cascade of signaling molecules that result in T cells, B cells, and 6774: 5910: 5713: 1694:

Pereira, TMC; Côco, LZ; Ton, AMM; Meyrelles, SS; Campos-Toimil, M; Campagnaro, BP; Vasquez, EC (20 November 2021).

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The process of neurodegeneration is not well understood, so the diseases that stem from it have, as yet, no cures.

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Apart from tubular structures, alpha-synuclein can also form lipoprotein nanoparticles similar to apolipoproteins.

6917: 6029: 4382:"Meta-analysis of genome-wide DNA methylation identifies shared associations across neurodegenerative disorders" 3815:

Lin MT, Beal MF (October 2006). "Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases".

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De Vos KJ, Grierson AJ, Ackerley S, Miller CC (2008). "Role of axonal transport in neurodegenerative diseases".

2009: 6912: 5544: 5520: 5350: 2222:"[P2–430]: Accuracy of Clinical Diagnosis of Alzheimer's Disease in Alzheimer's Disease Centers (ADCS)" 1888:

Rubinsztein DC (October 2006). "The roles of intracellular protein-degradation pathways in neurodegeneration".

529: 2688:"Invalid Self-Assessment of Olfactory Functioning in Parkinson's Disease Patients May Mislead the Neurologist" 389:

expansion in the huntingtin gene, resulting in the mutant huntingtin. Aggregates of mutant huntingtin form as

6890: 6615: 6223: 6108: 6024: 5966: 5736: 5515: 989: 851: 666: 644: 554: 461: 456: 93: 4330:"Pathogenic mechanisms of a polyglutamine-mediated neurodegenerative disease, spinocerebellar ataxia type 1" 3247:"Dissociated leg muscle atrophy in amyotrophic lateral sclerosis/motor neuron disease: the 'split-leg' sign" 6769: 6590: 6192: 5566: 2905: 299:

within affected neurons. It is thought that defects in protein transport machinery and regulation, such as

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in which a cell actively consumes damaged organelles or misfolded proteins by encapsulating them into an

6475: 5247:"Colorado doctor prescribes ping pong treatment for neurodegenerative disorders: 'Doing something good'" 3100: 3099:

Kaufman, David Myland; Milstein, Mark J. (2013-01-01), Kaufman, David Myland; Milstein, Mark J. (eds.),

1625:"Brain Basics: The Life and Death of a Neuron | National Institute of Neurological Disorders and Stroke" 6336: 6259: 6180: 5730: 5402: 1464: 525: 488:

protein aggregates have been implicated in some cases of the disease, and a mutation in chromosome 9 (

6779: 6648: 6130: 6098: 6072: 5899: 3076:"Multiple Sclerosis: Hope Through Research | National Institute of Neurological Disorders and Stroke" 969:, lipid concentration of the mitochondrial membranes, and the mitochondrial permeability transition. 757: 549: 228: 4519:"Oxidative Stress in Neurodegenerative Diseases: From Molecular Mechanisms to Clinical Applications" 3207: 1274:

Each of these neurodegenerative diseases have one (or several) specific main protein or peptide. In

6743: 6718: 6643: 6550: 6455: 6351: 6197: 5971: 5385: 5297: 4826:

Vila M, Przedborski S (May 2003). "Targeting programmed cell death in neurodegenerative diseases".

2583:"Membrane curvature induction and tubulation are common features of synucleins and apolipoproteins" 1051:. Defective DNA repair has been linked to neurodegenerative disorders such as Alzheimer's disease, 973:

leading to neurodegeneration is likely, at least on some level, to involve all of these functions.

623: 4279:"Unstable nucleotide repeat minireview series: a molecular biography of unstable repeat disorders" 3354:"Astrocytes expressing ALS-linked mutated SOD1 release factors selectively toxic to motor neurons" 6580: 6291: 6286: 6202: 6135: 5891: 5709: 5561: 5551: 5395: 2634:"Variants in GBA, SNCA, and MAPT influence Parkinson disease risk, age at onset, and progression" 1019: 1003: 950: 946: 788: 761: 693: 336: 331: 113: 109: 5314: 3736:"Creutzfeldt-Jakob Disease Fact Sheet | National Institute of Neurological Disorders and Stroke" 1167:

are other organelles that have damage sensors, which can lead the cells down apoptotic pathways.

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Masten MC, Williams JD, Vermilion J, Adams HR, Vierhile A, Collins A, et al. (June 2020).

3403:"Non-cell autonomous effect of glia on motor neurons in an embryonic stem cell-based ALS model" 3202: 1499: 1275: 1107: 954: 769: 697: 423: 265: 260: 216: 173: 168: 105: 101: 51: 20: 2488:

Elbaz A, Carcaillon L, Kab S, Moisan F (January 2016). "Epidemiology of Parkinson's disease".

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There are two main avenues eukaryotic cells use to remove troublesome proteins or organelles:

6878: 6638: 6633: 6440: 6331: 6252: 6082: 5956: 5774: 5752: 5667: 5590: 5500: 5487: 5412: 3352:

Nagai M, Re DB, Nagata T, Chalazonitis A, Jessell TM, Wichterle H, Przedborski S (May 2007).

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Purves D, Augustine GA, Fitzpatrick D, Hall W, LaMantia AS, McNamara JO, Williams SM (2001).

1472: 1330: 1309: 1118: 1064: 1056: 970: 962: 888: 419: 232: 401:. Huntington's disease currently has no effective treatments that would modify the disease. 6859: 6610: 6450: 6421: 6316: 6019: 5836: 5725: 5161: 5077: 4571:

Wang H, Dharmalingam P, Vasquez V, Mitra J, Boldogh I, Rao KS, et al. (January 2017).

4495: 4177: 4054: 3824: 3258: 2979: 2554: 1965: 1897: 966: 431: 3788:"Variant Creutzfeldt-Jakob Disease (vCJD) and Factor VIII (pdFVIII) Questions and Answers" 8: 6922: 6753: 6653: 6530: 6500: 6485: 5948: 5595: 5450: 5390: 2649: 2632:

Davis AA, Andruska KM, Benitez BA, Racette BA, Perlmutter JS, Cruchaga C (January 2016).

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or endoplasmic reticulum malfunctions, each leading to the activation of caspase-9. The

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disease, is a rare neurodegenerative disorder characterized by the gradual loss of both

227:(also written as A-beta or Aβ). Amyloid beta is a fragment from a larger protein called 139:

Within neurodegenerative diseases, it is estimated that 55 million people worldwide had

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advances against one neurodegenerative disease might ameliorate other diseases as well.

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Varkey J, Isas JM, Mizuno N, Jensen MB, Bhatia VK, Jao CC, et al. (October 2010).

2470: 2413: 2401: 2335: 2287: 2262: 2243: 2194: 2167: 1986: 1953: 1921: 1822: 1795: 1771: 1746: 1722: 1695: 1601: 1574: 1550: 1523: 1095: 1040: 565:(vCJD) is the infectious form that comes from the meat of a cow that was infected with 473: 469: 415: 410: 340: 311: 97: 2855:"Glial cells as intrinsic components of non-cell-autonomous neurodegenerative disease" 2686:

Schmidt, Nele; Paschen, Laura; Witt, Karsten (2020-11-16). Mirabella, Giovanni (ed.).

2323: 1845: 6748: 6683: 6658: 6510: 6470: 5881: 5847: 5819: 5810: 5742: 5718: 5585: 5433: 5228: 5177: 5126: 5091: 5034: 4952: 4900: 4843: 4808: 4757: 4708: 4654: 4602: 4550: 4499: 4464: 4413: 4361: 4310: 4259: 4207: 4195: 4143: 4082: 4070: 4041: 4026: 3971: 3922: 3871: 3840: 3721: 3682: 3653:"The CLN3 Disease Staging System: A new tool for clinical research in Batten disease" 3626: 3560:"Batten Disease Fact Sheet | National Institute of Neurological Disorders and Stroke" 3530: 3489: 3471: 3432: 3383: 3338: 3326: 3284: 3222: 3171: 3108: 3054: 3005: 2944: 2884: 2835: 2798: 2769: 2719: 2663: 2614: 2558: 2505: 2462: 2405: 2370: 2327: 2292: 2199: 2148: 2138: 2113: 2086: 2050: 2018: 1991: 1913: 1827: 1776: 1727: 1676: 1650: 1606: 1555: 1334: 1238: 1060: 268:(PD) is the second most common neurodegenerative disorder. It typically manifests as 59: 5138: 5046: 4964: 4855: 4694: 2474: 2417: 2339: 2247: 1345:

to each other and potentially to any other transglutaminase substrate in the brain.

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can aggregate to form insoluble fibrils in pathological conditions characterized by

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gene, which progressively increases its expression with age and has been related to

6789: 6673: 6600: 6515: 6396: 6346: 6004: 5875: 5870: 5655: 5650: 5218: 5208: 5169: 5118: 5081: 5073: 5026: 4998: 4944: 4890: 4882: 4835: 4798: 4788: 4747: 4739: 4698: 4690: 4644: 4636: 4592: 4584: 4540: 4530: 4491: 4454: 4444: 4403: 4393: 4351: 4341: 4300: 4290: 4249: 4239: 4185: 4133: 4123: 4062: 4016: 4006: 3961: 3953: 3912: 3904: 3852: 3832: 3709: 3672: 3664: 3616: 3608: 3597:"Therapeutic landscape for Batten disease: current treatments and future prospects" 3542: 3520: 3479: 3463: 3422: 3414: 3373: 3365: 3318: 3274: 3266: 3212: 3161: 3156: 3151: 3044: 3036: 2995: 2987: 2934: 2926: 2874: 2866: 2827: 2759: 2751: 2709: 2699: 2653: 2645: 2604: 2594: 2550: 2497: 2452: 2444: 2397: 2362: 2319: 2282: 2278: 2274: 2233: 2189: 2179: 2078: 2049:. Focus on structural biology. Dordrecht, Netherlands, New York, London: Springer. 1981: 1973: 1925: 1905: 1817: 1807: 1766: 1758: 1717: 1707: 1666: 1658: 1596: 1586: 1545: 1537: 1380: 1359: 1349: 1306: 1224: 1087: 1076: 999: 958: 742:. Protein toxicity is one of the key mechanisms of many neurodegenrative diseases. 654: 597: 394: 390: 280: 2523: 1573:

Lamptey RN, Chaulagain B, Trivedi R, Gothwal A, Layek B, Singh J (February 2022).

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The main known risk factor is age. Mutations in genes such as α-synuclein (SNCA),

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on left contrasted with structural changes shown in brain on right of person with

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Sweetlove M (2012). "Phase III CONCERT Trial of Latrepirdine. Negative results".

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Priller C, Bauer T, Mitteregger G, Krebs B, Kretzschmar HA, Herms J (July 2006).

1418: 1394: 1376: 1370: 1355: 1322: 1295: 1291: 1254: 1250: 1246: 1164: 1082: 985: 765: 747: 739: 499:

evidence that the primary cellular sites where SOD1 mutations act are located on

375: 344: 288: 244: 212: 205: 185: 5213: 3908: 3467: 2238: 2221: 1541: 6814: 6784: 6713: 6688: 6678: 6525: 6505: 6495: 6381: 6301: 5983: 5932: 5760: 5469: 5346: 5030: 4398: 4066: 3270: 3040: 2788: 1385:

abnormal structures that are characteristic of these neurodegenerative diseases

1342: 1287: 1242: 1126:

alternatively, PCD may occur in response to other injury or disease processes.

1122: 981: 977: 931: 928: 893: 818: 725: 674: 521: 516: 319: 248: 201: 121: 5122: 4948: 4588: 4449: 3891:

Maynard S, Fang EF, Scheibye-Knudsen M, Croteau DL, Bohr VA (September 2015).

3612: 3191:"Remyelination protects axons from demyelination-associated axon degeneration" 2448: 2263:"Synapse formation and function is modulated by the amyloid precursor protein" 1812: 1662: 1106:. When axonal transport is severely disrupted a degenerative pathway known as 6906: 6738: 6733: 6698: 6595: 6585: 6545: 6391: 6326: 6321: 6009: 5961: 5831: 5600: 5556: 5407: 4871:"Pharmacological manipulation of cell death: clinical applications in sight?" 4482:

DiMauro S, Schon EA (2008). "Mitochondrial disorders in the nervous system".

3475: 3025:"Huntington's disease: underlying molecular mechanisms and emerging concepts" 2152: 2090: 1524:"Clinical Neurology and Epidemiology of the Major Neurodegenerative Diseases" 1489: 1452: 1338: 1261: 1199: 840: 713: 504: 367: 197: 193: 129: 5291: 5287: 5173: 3995:"Virus exposure and neurodegenerative disease risk across national biobanks" 3957: 3713: 2991: 2599: 2082: 1649:

Patow, Gustavo; Escrichs, Anira; Ritter, Petra; Deco, Gustavo (2024-03-31).

1401:

has been detected in the autopsy of brains of patients with these diseases.

1267:

Most relevant human neurodegenerative diseases share the property of having

6824: 6819: 6703: 6535: 6460: 6411: 6401: 6376: 6371: 6341: 6275: 5505: 5375: 5358: 5232: 5130: 5095: 5038: 4956: 4904: 4847: 4812: 4761: 4712: 4658: 4606: 4554: 4535: 4503: 4468: 4417: 4365: 4346: 4314: 4295: 4263: 4244: 4199: 4147: 4074: 4030: 3975: 3926: 3844: 3686: 3630: 3534: 3493: 3436: 3387: 3330: 3288: 3226: 3217: 3190: 3175: 3058: 3009: 2948: 2888: 2839: 2773: 2723: 2704: 2667: 2618: 2562: 2509: 2466: 2409: 2374: 2331: 2296: 2203: 2117: 1995: 1917: 1831: 1780: 1731: 1712: 1680: 1610: 1559: 1468: 1436: 1422: 1314: 1279: 1231: 1195: 1160: 1156: 1103: 1099: 942: 843:, and they are primarily caused by aggregates in the following structures: 803: 363: 355: 276: 269: 224: 143:

in 2019, and that by 2050 this figure will increase to 139 million people.

5181: 4112:"Viruses in neurodegenerative diseases: More than just suspects in crimes" 2168:"Personalizing the Care and Treatment of Alzheimer's Disease: An Overview" 2132: 2070: 480:

were discovered in a subset of patients with familial ALS. More recently,

6693: 6540: 5464: 5425: 5367: 2184: 1591: 1007: 792: 784: 776: 753: 731: 583: 315: 296: 236: 125: 47: 5270: 4777:"Bacterial programmed cell death and multicellular behavior in bacteria" 3836: 1977: 1909: 176:(AD) is a chronic neurodegenerative disease that results in the loss of 6854: 6555: 5575: 5445: 5002: 3525: 3508: 2366: 2165: 1522:

Erkkinen, Michael G.; Kim, Mee-Ohk; Geschwind, Michael D (April 2018).

1326: 1299: 1175: 1036: 627: 485: 465: 439: 89: 68: 5015: 4774: 3322: 2755: 1762: 860:

extracellularly excreted proteins, amyloid-beta in Alzheimer's disease

6799: 6490: 5685: 5636: 5624: 5607: 5539: 4886: 4775:

Engelberg-Kulka H, Amitai S, Kolodkin-Gal I, Hazan R (October 2006).

4042:"Massive health-record review links viral illnesses to brain disease" 3401:

Di Giorgio FP, Carrasco MA, Siao MC, Maniatis T, Eggan K (May 2007).

3245:

Min YG, Choi SJ, Hong YH, Kim SM, Shin JY, Sung JJ (September 2020).

1439:

25–35. This suggests that there could be therapeutic value to PRP-1.

1134: 872: 716:

and increased tau pathology both in vitro and in mouse models of AD.

658: 500: 292: 117: 64: 4839: 4228:"Animal models of polyglutamine diseases and therapeutic approaches" 4190: 4165: 6708: 6160:

Spinal muscular atrophy with lower extremity predominance (SMALED)

5865: 5857: 5823: 5677: 5580: 5250: 3594: 3418: 3369: 2870: 1212: 1171: 1146: 678: 537: 533: 359: 284: 159: 140: 5062:"Active and passive immunotherapy for neurodegenerative disorders" 3890: 2817: 2134:

The Alzheimer conundrum : entanglements of dementia and aging

2104:

Wenk GL (2003). "Neuropathologic changes in Alzheimer's disease".

5344: 2736: 1796:"Oxidative Stress: A Key Modulator in Neurodegenerative Diseases" 1484: 1427: 1228: 1091: 1090:

can be disrupted by a variety of mechanisms including damage to:

1043:. Increased oxidative DNA damage in the brain is associated with 1018:

The brain metabolizes as much as a fifth of consumed oxygen, and

489: 240: 220: 189: 181: 133: 5108: 3105:

Kaufman's Clinical Neurology for Psychiatrists (Seventh Edition)

1241:

proteins and peptides intra- and intermolecularly, by a type of

6244: 5904: 5645: 5612: 5282: 3987: 3985: 3786:

Research, Center for Biologics Evaluation and (12 April 2019).

2387: 1745:

Stephenson, J; Nutma, E; van der Valk, P; Amor, S (June 2018).

1744: 1572: 1362: 995: 589: 481: 379: 177: 81: 4433:"Mechanisms of protein toxicity in neurodegenerative diseases" 3991: 3400: 2011:

Global status report on the public health response to dementia

808:

the major component of amyloid plaques in Alzheimer's disease.

791:

in Alzheimer's disease; tau fibrils are the main component of

626:

indicates that 45 (with 22 of these being replicated with the

287:. The cause of this selective cell death is unknown. Notably, 2309: 1027: 812: 709: 558: 397:, leading to impaired transport of important cargoes such as 358:. The first brain region to be substantially affected is the 307: 4934: 4570: 3982: 3650: 3308: 2540: 2260: 1002:

due to their strong metabolic activity associated with high

2964: 2631: 1794:

Singh, A; Kukreti, R; Saso, L; Kukreti, S (22 April 2019).

1174:(cysteine-aspartic acid proteases) cleave at very specific 588:

The greatest risk factor for neurodegenerative diseases is

477: 398: 300: 211:

AD pathology is primarily characterized by the presence of

6431: 3942:"Brain metabolism in health, aging, and neurodegeneration" 2047:

Protein folding and misfolding: neurodegenerative diseases

1234:

present in the human body and in the brain in particular.

132:) and induced cell death. These similarities suggest that 3351: 1318: 1283: 1031: 618:

Risks from viral exposures according to one biobank study

4225: 2487: 4516: 2433:"Amyloid fibrils from the viewpoint of protein folding" 1793: 1693: 1648: 1022:

produced by oxidative metabolism are a major source of

665:. Diseases associated with such mutations are known as 295:

complexes and aggregates are observed to accumulate in

188:

and certain subcortical structures, resulting in gross

5151: 4517:

Liu Z, Zhou T, Ziegler AC, Dimitrion P, Zuo L (2017).

3893:"DNA Damage, DNA Repair, Aging, and Neurodegeneration" 2580: 1417:

In the search for effective treatments (as opposed to

343:

neurodegenerative disorder caused by mutations in the

88:. Neuronal damage may also ultimately result in their 4676: 4378: 3140:"Recent advances in understanding multiple sclerosis" 730:

Several neurodegenerative diseases are classified as

223:, typically 39–43 amino acids in length, called 5260: 2968:"Huntington's disease alters human neurodevelopment" 2797:(2nd ed.). Sunderland, MA: Sinauer Associates. 1521: 1426:

ameliorate disease severity. An example is the drug

1269:

abnormal structures made up of proteins and peptides

4226:Marsh JL, Lukacsovich T, Thompson LM (March 2009). 2002: 128:level, including atypical protein assemblies (like 5197:"Treatment strategies targeting amyloid β-protein" 5194: 4040: 3865: 2685: 5195:Schenk D, Basi GS, Pangalos MN (September 2012). 4622: 4110:Leblanc, Pascal; Vorberg, Ina Maja (2022-08-04). 3762:"Creutzfeldt-Jakob disease - Symptoms and causes" 3107:, Philadelphia: W.B. Saunders, pp. 329–349, 2852: 1951: 1442: 503:. Astrocytes then cause the toxic effects on the 6904: 3939: 3449: 3070: 3068: 3022: 2219: 1747:"Inflammation in CNS neurodegenerative diseases" 450: 4825: 4677:Jeppesen DK, Bohr VA, Stevnsner T (July 2011). 4672: 4670: 4668: 4625:"DNA damage and its links to neurodegeneration" 4618: 4616: 4566: 4564: 3870:. San Diego: Academic Press. pp. 121–139. 3188: 3138:Stys, Peter K.; Tsutsui, Shigeki (2019-12-13). 3098: 2681: 2679: 2677: 834: 4725: 4109: 3646: 3644: 3642: 3640: 3244: 2960: 2958: 2215: 2213: 1952:Bredesen DE, Rao RV, Mehlen P (October 2006). 1495:Neurodegeneration with brain iron accumulation 1471:for patients who are suffering from a serious 653:Many neurodegenerative diseases are caused by 6260: 5330: 5059: 4431:Chung, CG; Lee, H; Lee, SB (September 2018). 3859: 3509:"ALS: astrocytes move in as deadly neighbors" 3450:Phatnani, Hemali; Maniatis, Tom (June 2015). 3304: 3302: 3300: 3298: 3065: 2430: 1883: 1881: 1879: 1877: 1875: 1873: 1871: 1869: 1867: 1517: 1515: 1393:Co-localization of transglutaminase mediated 876:primary route cells use to degrade proteins. 6795:Intraoperative neurophysiological monitoring 4868: 4679:"DNA repair deficiency in neurodegeneration" 4665: 4613: 4561: 4510: 4481: 3933: 3884: 3590: 3588: 3586: 3584: 3582: 3580: 3133: 3131: 3129: 2910: 2846: 2811: 2674: 2625: 2576: 2574: 2572: 2522:"Parkinson's Disease Mechanism Discovered," 2424: 2381: 2346: 2303: 2254: 2097: 1412: 936: 543: 6049: 5201:Cold Spring Harbor Perspectives in Medicine 4982: 4728:"Wallerian degeneration, wld(s), and nmnat" 4430: 4159: 4157: 3897:Cold Spring Harbor Perspectives in Medicine 3700:Hartnett L (2019-09-30). "Batten disease". 3637: 3240: 3238: 3236: 3137: 2955: 2853:Lobsiger CS, Cleveland DW (November 2007). 2210: 2017:. Geneva: World Health Organization. 2021. 1947: 1945: 1943: 1941: 1939: 1937: 1935: 1887: 1178:residues. There are two types of caspases: 829: 54:, the most common neurodegenerative disease 6267: 6253: 5337: 5323: 4930: 4928: 4926: 4924: 4922: 4920: 4918: 4916: 4914: 4623:Madabhushi R, Pan L, Tsai LH (July 2014). 4166:"Neurodegeneration: a question of balance" 3456:Cold Spring Harbor Perspectives in Biology 3295: 2919:"Functional anatomy of movement disorders" 2789:"Circuits within the Basal Ganglia System" 2172:Pharmacogenomics and Personalized Medicine 2044: 1864: 1529:Cold Spring Harbor Perspectives in Biology 1512: 1337:in vitro or in vivo, that is, they can be 1237:The main function of transglutaminases is 1006:levels, high oxygen consumption, and weak 847:cytosol, e.g. Parkinson's and Huntington's 797:behavioral variant frontotemporal dementia 275:PD is primarily characterized by death of 37: 5222: 5212: 5085: 4988: 4894: 4802: 4792: 4768: 4751: 4702: 4648: 4596: 4544: 4534: 4523:Oxidative Medicine and Cellular Longevity 4458: 4448: 4407: 4397: 4355: 4345: 4327: 4304: 4294: 4253: 4243: 4189: 4137: 4127: 4020: 4010: 3965: 3916: 3676: 3620: 3577: 3524: 3483: 3452:"Astrocytes in Neurodegenerative Disease" 3426: 3394: 3377: 3278: 3216: 3206: 3165: 3155: 3126: 3048: 2999: 2938: 2878: 2763: 2713: 2703: 2657: 2608: 2598: 2569: 2456: 2286: 2237: 2193: 2183: 1985: 1821: 1811: 1770: 1738: 1721: 1711: 1670: 1600: 1590: 1549: 1205: 649:Epigenetics of neurodegenerative diseases 4221: 4219: 4217: 4163: 4154: 3785: 3699: 3233: 3189:Irvine, K. A.; Blakemore, W. F. (2008). 2916: 2536: 2534: 2532: 1932: 1113: 613: 158: 5009: 4911: 4475: 3814: 3023:Labbadia J, Morimoto RI (August 2013). 1189: 823:transmissible spongiform encephalopathy 325: 6905: 6126:Distal hereditary motor neuronopathies 5799:Template:Demyelinating diseases of CNS 5078:10.1146/annurev.neuro.31.060407.125529 4819: 4496:10.1146/annurev.neuro.30.051606.094302 4038: 3810: 3808: 3554: 3552: 3506: 3500: 2901: 2786: 2555:10.1146/annurev.neuro.31.061307.090711 2352: 2220:Archer MC, Hall PH, Morgan JC (2017). 1687: 1566: 254: 154: 6248: 5318: 5053: 4875:The Journal of Clinical Investigation 4862: 4424: 4214: 3940:Camandola S, Mattson MP (June 2017). 3345: 2529: 1194:Autophagy is a form of intracellular 1155:Result from mitochondrial release of 1129: 719: 404: 146: 92:. Neurodegenerative diseases include 80:is caused by the progressive loss of 6885: 5977:Idiopathic intracranial hypertension 5366: 5111:Molecular and Cellular Neurosciences 4978:Dimebon Disappoints in Phase 3 Trial 4869:Green DR, Kroemer G (October 2005). 4577:Mechanisms of Ageing and Development 4437:Cellular and Molecular Life Sciences 4089:from the original on 6 February 2023 2650:10.1016/j.neurobiolaging.2015.09.014 2437:Cellular and Molecular Life Sciences 2130: 2103: 2045:Ovádi, Judit; Orosz, Ferenc (2009). 1846:"What is Neurodegenerative Disease?" 1787: 1617: 1383:reaction) have been detected in the 4744:10.1146/annurev-neuro-060909-153248 4334:The Journal of Biological Chemistry 4283:The Journal of Biological Chemistry 4276: 4270: 4232:The Journal of Biological Chemistry 3805: 3549: 2931:10.1046/j.1469-7580.2000.19640519.x 2587:The Journal of Biological Chemistry 1838: 1219: 1070: 482:TAR DNA-binding protein 43 (TDP-43) 428:myelin oligodendrocyte glycoprotein 13: 6208:Infantile progressive bulbar palsy 2431:Ohnishi S, Takano K (March 2004). 2402:10.1212/01.WNL.0000129697.01779.0A 2106:The Journal of Clinical Psychiatry 1954:"Cell death in the nervous system" 921: 899:chaperone-mediated autophagy (CMA) 362:, followed by degeneration of the 14: 6939: 6775:Development of the nervous system 5911:Template:Cerebrovascular diseases 5714:Frontotemporal lobar degeneration 3866:Bernstein C, Bernstein H (1991). 3101:"Chapter 15 - Multiple Sclerosis" 947:mitochondrial intermembrane space 689:), mice, and non-human primates. 563:Variant Creutzfeldt–Jakob disease 510: 350:. HD is characterized by loss of 6884: 6873: 6872: 6430: 6274: 5931:For more detailed coverage, see 5909:For more detailed coverage, see 5880:For more detailed coverage, see 5846:For more detailed coverage, see 5797:For more detailed coverage, see 4328:Zoghbi HY, Orr HT (March 2009). 2355:Biochemical Society Transactions 2075:Cell Biochemistry and Biophysics 734:as they are associated with the 567:bovine spongiform encephalopathy 5239: 5188: 5145: 5102: 4971: 4726:Coleman MP, Freeman MR (2010). 4719: 4695:10.1016/j.pneurobio.2011.04.013 4372: 4321: 4103: 4039:Kozlov, Max (23 January 2023). 3779: 3754: 3728: 3693: 3443: 3182: 3092: 3016: 2895: 2780: 2730: 2516: 2481: 2159: 2124: 2063: 2038: 998:are particularly vulnerable to 756:, such as Parkinson's disease, 661:. A repeat of CAG results in a 572: 569:, also called mad cow disease. 418:(MS) is a chronic debilitating 219:. Plaques are made up of small 5060:Brody DL, Holtzman DM (2008). 4037:News article about the study: 3742:. National Institute of Health 3157:10.12688/f1000research.20906.1 3029:Trends in Biochemical Sciences 2279:10.1523/JNEUROSCI.1450-06.2006 2137:. Princeton University Press. 1642: 1463:Dr. Antonio Barbera, a former 1448:only beginning to understand. 1443:Other avenues of investigation 703: 667:trinucleotide repeat disorders 530:neuronal ceroid lipofuscinoses 495:Independent research provided 16:Central nervous system disease 1: 6616:Social cognitive neuroscience 6224:Amyotrophic lateral sclerosis 6109:Hereditary spastic paraplegia 5967:Normal pressure hydrocephalus 5066:Annual Review of Neuroscience 4484:Annual Review of Neuroscience 2543:Annual Review of Neuroscience 2324:10.1016/S0301-0082(03)00089-3 1505: 1404: 1153:Intrinsic apoptotic pathways: 1143:Extrinsic apoptotic pathways: 1053:amyotrophic lateral sclerosis 1035:decline in the activities of 1013: 990:amyotrophic lateral sclerosis 852:Spinocerebellar ataxia type 1 645:Trinucleotide repeat disorder 633: 609: 478:superoxide dismutase 1 (SOD1) 462:Amyotrophic lateral sclerosis 457:Amyotrophic lateral sclerosis 451:Amyotrophic lateral sclerosis 94:amyotrophic lateral sclerosis 19:For the medical journal, see 6591:Molecular cellular cognition 6193:Progressive muscular atrophy 4828:Nature Reviews. Neuroscience 4794:10.1371/journal.pgen.0020135 4641:10.1016/j.neuron.2014.06.034 4129:10.1371/journal.ppat.1010670 4012:10.1016/j.neuron.2022.12.029 3702:Learning Disability Practice 3669:10.1212/WNL.0000000000009454 2832:10.1016/j.arcmed.2007.11.011 2820:Archives of Medical Research 2502:10.1016/j.neurol.2015.09.012 912:chaperone-mediated autophagy 885:autophagy–lysosome pathways: 835:Protein degradation pathways 464:(ALS), commonly referred to 374:send control signals to the 308:leucine-rich repeat kinase 2 7: 6928:Neurodegenerative disorders 6810:Neurodevelopmental disorder 6785:Neural network (biological) 6780:Neural network (artificial) 5703:Primary progressive aphasia 5214:10.1101/cshperspect.a006387 3909:10.1101/cshperspect.a025130 3468:10.1101/cshperspect.a020628 2925:. 196 ( Pt 4) (4): 519–25. 2906:Box A. Huntington's Disease 2267:The Journal of Neuroscience 2239:10.1016/j.jalz.2017.06.1086 2131:Lock MM (27 October 2013). 1542:10.1101/cshperspect.a033118 1478: 1108:Wallerian-like degeneration 663:polyglutamine (polyQ) tract 638: 594:Mitochondrial DNA mutations 526:lysosomal storage disorders 10: 6944: 6337:Computational neuroscience 6025:Hashimoto's encephalopathy 5731:Posterior cortical atrophy 5552:Striatonigral degeneration 5403:Cavernous sinus thrombosis 5031:10.1016/j.jalz.2007.10.019 5019:Alzheimer's & Dementia 4399:10.1186/s13059-021-02275-5 4164:Thompson LM (April 2008). 4067:10.1038/d41586-023-00181-3 3868:Aging, Sex, and DNA Repair 3271:10.1038/s41598-020-72887-7 3041:10.1016/j.tibs.2013.05.003 2226:Alzheimer's & Dementia 1465:obstetrics and gynaecology 1074: 1063:, Parkinson's disease and 957:. Over production of ROS ( 723: 642: 581: 547: 514: 454: 408: 329: 258: 239:into smaller fragments by 166: 84:, in the process known as 18: 6868: 6805:Neurodegenerative disease 6762: 6649:Evolutionary neuroscience 6624: 6564: 6439: 6428: 6300: 6282: 6131:Spinal muscular atrophies 6099:Primary lateral sclerosis 6081: 6058: 6042: 5997: 5957:Intracranial hypertension 5947: 5919: 5890: 5856: 5818: 5807: 5773: 5751: 5737:Creutzfeldt–Jakob disease 5676: 5486: 5477: 5463: 5423: 5357: 5264: 5123:10.1016/j.mcn.2003.12.013 4949:10.1007/s00726-009-0428-3 4589:10.1016/j.mad.2016.09.005 4450:10.1007/s00018-018-2854-4 3613:10.1038/s41582-019-0138-8 2449:10.1007/s00018-003-3264-8 1813:10.3390/molecules24081583 1663:10.1101/2024.03.29.587333 1413:Animal models in research 937:Mitochondrial dysfunction 787:is the main component of 758:dementia with Lewy bodies 624:electronic health records 555:Creutzfeldt–Jakob disease 550:Creutzfeldt-Jakob disease 544:Creutzfeldt–Jakob disease 370:cortices. The striatum's 229:amyloid precursor protein 78:neurodegenerative disease 58: 45: 36: 32:Neurodegenerative disease 31: 6770:Brain–computer interface 6719:Neuromorphic engineering 6644:Educational neuroscience 6551:Nutritional neuroscience 6456:Clinical neurophysiology 6352:Integrative neuroscience 6198:Progressive bulbar palsy 5989:Intracranial hypotension 5972:Choroid plexus papilloma 5386:Herpesviral encephalitis 4683:Progress in Neurobiology 3601:Nature Reviews Neurology 2917:Crossman AR (May 2000). 2312:Progress in Neurobiology 1421:), investigators employ 830:Intracellular mechanisms 577: 6581:Behavioral neuroscience 5710:Frontotemporal dementia 5396:Encephalitis lethargica 5174:10.1126/science.2111583 3958:10.15252/embj.201695810 3714:10.7748/ldp.22.5.22.s16 2992:10.1126/science.aax3338 2600:10.1074/jbc.M110.139576 2083:10.1007/12013.1559-0283 1467:doctor, is prescribing 1341:by trasglutaminases by 1329:have been proved to be 1249:, in a reaction termed 1020:reactive oxygen species 951:Reactive oxygen species 789:neurofibrillary tangles 762:multiple system atrophy 698:spinocerebellar ataxias 217:neurofibrillary tangles 114:multiple system atrophy 6918:Neurological disorders 6576:Affective neuroscience 6357:Molecular neuroscience 6312:Behavioral epigenetics 6015:Hepatic encephalopathy 4347:10.1074/jbc.R800041200 4296:10.1074/jbc.R800067200 4245:10.1074/jbc.R800065200 3507:Julien JP (May 2007). 1713:10.3390/antiox10111845 1500:Prevention of dementia 1206:Cytoplasmic (type III) 955:glutathione peroxidase 619: 486:Fused in Sarcoma (FUS) 424:central nervous system 164: 21:Experimental Neurology 6913:Clinical neuroscience 6639:Cultural neuroscience 6634:Consumer neuroscience 6476:Neurogastroenterology 6332:Cellular neuroscience 6073:Ataxia–telangiectasia 6030:Static encephalopathy 5753:Mitochondrial disease 5591:Spasmodic torticollis 5501:Basal ganglia disease 4277:Orr HT (March 2009). 2791:. In Purves D (ed.). 2638:Neurobiology of Aging 2232:(7S_Part_16): 800–1. 1657:: 2024.03.29.587333. 1473:neurological disorder 1352:augmented expression: 1119:Programmed cell death 1114:Programmed cell death 1081:Axonal swelling, and 1065:xeroderma pigmentosum 1057:ataxia telangiectasia 1030:. Damage to a cell's 971:Mitochondrial disease 963:mitochondrial fission 889:programmed cell death 869:ubiquitin–proteasome: 617: 582:Further information: 420:demyelinating disease 233:transmembrane protein 162: 6611:Sensory neuroscience 6451:Behavioral neurology 6422:Systems neuroscience 6020:Toxic encephalopathy 5726:Lewy bodies dementia 4536:10.1155/2017/2525967 3218:10.1093/brain/awn080 2705:10.1155/2020/7548394 2185:10.2147/PGPM.S284615 1592:10.3390/ijms23031851 1373:in these structures: 1190:Autophagic (type II) 1121:(PCD) is death of a 1110:is often triggered. 694:Huntington's disease 432:myelin basic protein 352:medium spiny neurons 337:Huntington's disease 332:Huntington's disease 326:Huntington's disease 110:Huntington's disease 6754:Social neuroscience 6654:Global neurosurgery 6531:Neurorehabilitation 6501:Neuro-ophthalmology 6486:Neurointensive care 6317:Behavioral genetics 6068:Friedreich's ataxia 5451:Meningoencephalitis 5391:Limbic encephalitis 5253:. January 12, 2024. 5166:1990Sci...248.1122E 4182:2008Natur.452..707T 4059:2023Natur.614...18K 3837:10.1038/nature05292 3829:2006Natur.443..787L 3663:(23): e2436–e2440. 3513:Nature Neuroscience 3407:Nature Neuroscience 3358:Nature Neuroscience 3263:2020NatSR..1015661M 2984:2020Sci...369..787B 2859:Nature Neuroscience 2692:Parkinson's Disease 2071:"Journal home page" 1978:10.1038/nature05293 1970:2006Natur.443..796B 1910:10.1038/nature05291 1902:2006Natur.443..780R 1399:abnormal structures 1379:(the result of the 1276:Alzheimer's disease 1049:Parkinson's disease 1045:Alzheimer's disease 782:hyperphosphorylated 770:Alzheimer's disease 474:lower motor neurons 470:upper motor neurons 436:proteolipid protein 387:polyglutamine tract 266:Parkinson's disease 261:Parkinson's disease 255:Parkinson's disease 200:, and parts of the 174:Alzheimer's disease 169:Alzheimer's disease 155:Alzheimer's disease 106:Alzheimer's disease 102:Parkinson's disease 52:Alzheimer's disease 6830:Neuroimmune system 6724:Neurophenomenology 6664:Neural engineering 6387:Neuroendocrinology 6367:Neural engineering 6104:Pseudobulbar palsy 5842:Status epilepticus 5793:Multiple sclerosis 5630:Myoclonic epilepsy 5493:movement disorders 5439:Acute disseminated 5381:Viral encephalitis 5003:10.1007/BF03256900 3526:10.1038/nn0507-535 3311:Muscle & Nerve 3251:Scientific Reports 2923:Journal of Anatomy 2744:Movement Disorders 2524:HHMI Research News 2490:Revue Neurologique 2367:10.1042/BST0330335 1130:Apoptosis (type I) 1096:cytoplasmic dynein 1041:oculomotor apraxia 908:neurodegeneration. 817:main component of 740:misfolded proteins 720:Protein misfolding 685:), and fruit fly ( 620: 416:Multiple sclerosis 411:Multiple sclerosis 405:Multiple sclerosis 372:subthalamic nuclei 341:autosomal dominant 312:glucocerebrosidase 283:, a region of the 165: 147:Specific disorders 98:multiple sclerosis 6900: 6899: 6749:Paleoneurobiology 6684:Neuroepistemology 6659:Neuroanthropology 6625:Interdisciplinary 6511:Neuropharmacology 6471:Neuroepidemiology 6242: 6241: 6238: 6237: 6234: 6233: 6038: 6037: 5943: 5942: 5882:Template:Headache 5848:Template:Epilepsy 5769: 5768: 5743:Vascular dementia 5586:Status dystonicus 5459: 5458: 5434:Encephalomyelitis 5312: 5311: 4732:Annu Rev Neurosci 4583:(Pt A): 163–176. 4005:(7): 1086–93.e2. 3877:978-0-12-092860-6 3740:www.ninds.nih.gov 3564:www.ninds.nih.gov 3323:10.1002/mus.26764 3114:978-0-7234-3748-2 3080:www.ninds.nih.gov 2978:(6505): 787–793. 2804:978-0-87893-742-4 2756:10.1002/mds.26942 2644:: 209.e1–209.e7. 2144:978-1-4008-4846-1 2112:(Suppl 9): 7–10. 2056:978-1-4020-9434-7 2024:978-92-4-003324-5 1964:(7113): 796–802. 1763:10.1111/imm.12922 1629:www.ninds.nih.gov 1335:transglutaminases 1260:Transglutaminase 1225:Transglutaminases 1061:Cockayne syndrome 1037:repair mechanisms 655:genetic mutations 86:neurodegeneration 74: 73: 26:Medical condition 6935: 6888: 6887: 6876: 6875: 6790:Detection theory 6674:Neurocriminology 6601:Neurolinguistics 6516:Neuroprosthetics 6434: 6397:Neuroinformatics 6347:Imaging genetics 6269: 6262: 6255: 6246: 6245: 6056: 6055: 6047: 6046: 6005:Brain herniation 5816: 5815: 5656:Intention tremor 5651:Essential tremor 5516:Postencephalitic 5484: 5483: 5475: 5474: 5364: 5363: 5345:Diseases of the 5339: 5332: 5325: 5316: 5315: 5262: 5261: 5255: 5254: 5243: 5237: 5236: 5226: 5216: 5192: 5186: 5185: 5160:(4959): 1122–4. 5149: 5143: 5142: 5106: 5100: 5099: 5089: 5057: 5051: 5050: 5013: 5007: 5006: 4986: 4980: 4975: 4969: 4968: 4932: 4909: 4908: 4898: 4887:10.1172/JCI26321 4866: 4860: 4859: 4823: 4817: 4816: 4806: 4796: 4772: 4766: 4765: 4755: 4723: 4717: 4716: 4706: 4674: 4663: 4662: 4652: 4620: 4611: 4610: 4600: 4568: 4559: 4558: 4548: 4538: 4514: 4508: 4507: 4479: 4473: 4472: 4462: 4452: 4428: 4422: 4421: 4411: 4401: 4376: 4370: 4369: 4359: 4349: 4325: 4319: 4318: 4308: 4298: 4274: 4268: 4267: 4257: 4247: 4223: 4212: 4211: 4193: 4161: 4152: 4151: 4141: 4131: 4107: 4101: 4098: 4096: 4094: 4044: 4034: 4024: 4014: 3989: 3980: 3979: 3969: 3946:The EMBO Journal 3937: 3931: 3930: 3920: 3888: 3882: 3881: 3863: 3857: 3856: 3823:(7113): 787–95. 3812: 3803: 3802: 3800: 3798: 3783: 3777: 3776: 3774: 3772: 3758: 3752: 3751: 3749: 3747: 3732: 3726: 3725: 3697: 3691: 3690: 3680: 3648: 3635: 3634: 3624: 3592: 3575: 3574: 3572: 3570: 3556: 3547: 3546: 3528: 3504: 3498: 3497: 3487: 3447: 3441: 3440: 3430: 3398: 3392: 3391: 3381: 3349: 3343: 3342: 3306: 3293: 3292: 3282: 3242: 3231: 3230: 3220: 3210: 3186: 3180: 3179: 3169: 3159: 3135: 3124: 3123: 3122: 3121: 3096: 3090: 3089: 3087: 3086: 3072: 3063: 3062: 3052: 3020: 3014: 3013: 3003: 2962: 2953: 2952: 2942: 2914: 2908: 2899: 2893: 2892: 2882: 2850: 2844: 2843: 2815: 2809: 2808: 2784: 2778: 2777: 2767: 2734: 2728: 2727: 2717: 2707: 2683: 2672: 2671: 2661: 2629: 2623: 2622: 2612: 2602: 2593:(42): 32486–93. 2578: 2567: 2566: 2538: 2527: 2520: 2514: 2513: 2485: 2479: 2478: 2460: 2428: 2422: 2421: 2385: 2379: 2378: 2350: 2344: 2343: 2307: 2301: 2300: 2290: 2258: 2252: 2251: 2241: 2217: 2208: 2207: 2197: 2187: 2163: 2157: 2156: 2128: 2122: 2121: 2101: 2095: 2094: 2067: 2061: 2060: 2042: 2036: 2035: 2033: 2031: 2016: 2006: 2000: 1999: 1989: 1949: 1930: 1929: 1885: 1862: 1861: 1859: 1857: 1842: 1836: 1835: 1825: 1815: 1791: 1785: 1784: 1774: 1742: 1736: 1735: 1725: 1715: 1691: 1685: 1684: 1674: 1646: 1640: 1639: 1637: 1635: 1621: 1615: 1614: 1604: 1594: 1570: 1564: 1563: 1553: 1519: 1395:isopeptide bonds 1391:Co-localization: 1381:transglutaminase 1377:isopeptide bonds 1375:The presence of 1371:isopeptide bonds 1360:transglutaminase 1350:Transglutaminase 1307:Transglutaminase 1247:isopeptide bonds 1220:Transglutaminase 1088:Axonal transport 1083:axonal spheroids 1077:Axonal transport 1071:Axonal transport 1000:oxidative damage 959:oxidative stress 598:oxidative stress 395:axonal transport 391:inclusion bodies 385:HD is caused by 281:substantia nigra 41: 29: 28: 6943: 6942: 6938: 6937: 6936: 6934: 6933: 6932: 6903: 6902: 6901: 6896: 6864: 6850:Neurotechnology 6845:Neuroplasticity 6840:Neuromodulation 6835:Neuromanagement 6758: 6729:Neurophilosophy 6626: 6620: 6606:Neuropsychology 6567: 6560: 6521:Neuropsychiatry 6481:Neuroimmunology 6466:Neurocardiology 6442: 6435: 6426: 6417:Neurophysiology 6407:Neuromorphology 6362:Neural decoding 6303: 6296: 6278: 6273: 6243: 6230: 6156:Congenital DSMA 6077: 6034: 5993: 5939: 5927:Sleep disorders 5915: 5892:Cerebrovascular 5886: 5852: 5809: 5803: 5765: 5747: 5672: 5618:Choreoathetosis 5491: 5468: 5455: 5419: 5353: 5343: 5313: 5308: 5307: 5273: 5259: 5258: 5245: 5244: 5240: 5193: 5189: 5150: 5146: 5107: 5103: 5058: 5054: 5014: 5010: 4987: 4983: 4976: 4972: 4933: 4912: 4867: 4863: 4840:10.1038/nrn1100 4824: 4820: 4773: 4769: 4724: 4720: 4675: 4666: 4621: 4614: 4569: 4562: 4515: 4511: 4480: 4476: 4443:(17): 3159–80. 4429: 4425: 4377: 4373: 4326: 4322: 4275: 4271: 4224: 4215: 4191:10.1038/452707a 4176:(7188): 707–8. 4162: 4155: 4122:(8): e1010670. 4108: 4104: 4092: 4090: 4053:(7946): 18–19. 3990: 3983: 3952:(11): 1474–92. 3938: 3934: 3903:(10): a025130. 3889: 3885: 3878: 3864: 3860: 3813: 3806: 3796: 3794: 3784: 3780: 3770: 3768: 3760: 3759: 3755: 3745: 3743: 3734: 3733: 3729: 3698: 3694: 3649: 3638: 3593: 3578: 3568: 3566: 3558: 3557: 3550: 3505: 3501: 3448: 3444: 3399: 3395: 3350: 3346: 3307: 3296: 3243: 3234: 3208:10.1.1.328.2931 3187: 3183: 3136: 3127: 3119: 3117: 3115: 3097: 3093: 3084: 3082: 3074: 3073: 3066: 3021: 3017: 2963: 2956: 2915: 2911: 2900: 2896: 2865:(11): 1355–60. 2851: 2847: 2816: 2812: 2805: 2785: 2781: 2735: 2731: 2684: 2675: 2630: 2626: 2579: 2570: 2539: 2530: 2521: 2517: 2486: 2482: 2429: 2425: 2386: 2382: 2361:(Pt 2): 335–8. 2351: 2347: 2308: 2304: 2273:(27): 7212–21. 2259: 2255: 2218: 2211: 2164: 2160: 2145: 2129: 2125: 2102: 2098: 2069: 2068: 2064: 2057: 2043: 2039: 2029: 2027: 2025: 2014: 2008: 2007: 2003: 1950: 1933: 1896:(7113): 780–6. 1886: 1865: 1855: 1853: 1844: 1843: 1839: 1792: 1788: 1743: 1739: 1692: 1688: 1647: 1643: 1633: 1631: 1623: 1622: 1618: 1571: 1567: 1520: 1513: 1508: 1481: 1445: 1419:palliative care 1415: 1407: 1323:alpha-synuclein 1298:disease, it is 1292:alpha-synuclein 1290:disease, it is 1222: 1208: 1192: 1165:Golgi apparatus 1132: 1116: 1102:, cargoes, and 1079: 1073: 1016: 939: 924: 922:Membrane damage 837: 832: 766:amyloid plaques 748:alpha-synuclein 728: 722: 706: 651: 641: 636: 612: 586: 580: 575: 552: 546: 519: 513: 459: 453: 413: 407: 376:globus pallidus 345:huntingtin gene 339:(HD) is a rare 334: 328: 289:alpha-synuclein 279:neurons in the 263: 257: 245:gamma secretase 213:amyloid plaques 206:cingulate gyrus 186:cerebral cortex 171: 157: 149: 27: 24: 17: 12: 11: 5: 6941: 6931: 6930: 6925: 6920: 6915: 6898: 6897: 6895: 6894: 6882: 6869: 6866: 6865: 6863: 6862: 6860:Self-awareness 6857: 6852: 6847: 6842: 6837: 6832: 6827: 6822: 6817: 6815:Neurodiversity 6812: 6807: 6802: 6797: 6792: 6787: 6782: 6777: 6772: 6766: 6764: 6760: 6759: 6757: 6756: 6751: 6746: 6741: 6736: 6731: 6726: 6721: 6716: 6714:Neuromarketing 6711: 6706: 6701: 6696: 6691: 6689:Neuroesthetics 6686: 6681: 6679:Neuroeconomics 6676: 6671: 6666: 6661: 6656: 6651: 6646: 6641: 6636: 6630: 6628: 6622: 6621: 6619: 6618: 6613: 6608: 6603: 6598: 6593: 6588: 6583: 6578: 6572: 6570: 6562: 6561: 6559: 6558: 6553: 6548: 6543: 6538: 6533: 6528: 6526:Neuroradiology 6523: 6518: 6513: 6508: 6506:Neuropathology 6503: 6498: 6496:Neuro-oncology 6493: 6488: 6483: 6478: 6473: 6468: 6463: 6458: 6453: 6447: 6445: 6437: 6436: 6429: 6427: 6425: 6424: 6419: 6414: 6409: 6404: 6399: 6394: 6389: 6384: 6382:Neurochemistry 6379: 6374: 6369: 6364: 6359: 6354: 6349: 6344: 6339: 6334: 6329: 6324: 6319: 6314: 6308: 6306: 6298: 6297: 6295: 6294: 6289: 6283: 6280: 6279: 6272: 6271: 6264: 6257: 6249: 6240: 6239: 6236: 6235: 6232: 6231: 6229: 6228: 6227: 6226: 6215: 6214: 6213: 6212: 6211: 6210: 6205: 6195: 6190: 6189: 6188: 6183: 6178: 6177: 6176: 6171: 6166: 6158: 6153: 6148: 6143: 6138: 6128: 6114: 6113: 6112: 6111: 6106: 6101: 6087: 6085: 6079: 6078: 6076: 6075: 6070: 6064: 6062: 6053: 6044: 6040: 6039: 6036: 6035: 6033: 6032: 6027: 6022: 6017: 6012: 6007: 6001: 5999: 5995: 5994: 5992: 5991: 5986: 5984:Cerebral edema 5981: 5980: 5979: 5974: 5969: 5964: 5953: 5951: 5945: 5944: 5941: 5940: 5938: 5937: 5936: 5935: 5933:Template:Sleep 5923: 5921: 5917: 5916: 5914: 5913: 5907: 5902: 5896: 5894: 5888: 5887: 5885: 5884: 5878: 5873: 5868: 5862: 5860: 5854: 5853: 5851: 5850: 5844: 5839: 5834: 5828: 5826: 5813: 5805: 5804: 5802: 5801: 5795: 5790: 5785: 5779: 5777: 5771: 5770: 5767: 5766: 5764: 5763: 5761:Leigh syndrome 5757: 5755: 5749: 5748: 5746: 5745: 5734: 5733: 5728: 5723: 5722: 5721: 5707: 5706: 5705: 5700: 5699: 5698: 5682: 5680: 5674: 5673: 5671: 5670: 5665: 5660: 5659: 5658: 5653: 5642: 5641: 5640: 5639: 5634: 5633: 5632: 5622: 5621: 5620: 5610: 5605: 5604: 5603: 5598: 5593: 5588: 5572: 5571: 5570: 5569: 5564: 5559: 5554: 5549: 5548: 5547: 5537: 5536: 5535: 5525: 5524: 5523: 5518: 5513: 5497: 5495: 5488:Extrapyramidal 5481: 5472: 5470:encephalopathy 5461: 5460: 5457: 5456: 5454: 5453: 5448: 5443: 5442: 5441: 5430: 5428: 5421: 5420: 5418: 5417: 5416: 5415: 5405: 5400: 5399: 5398: 5393: 5388: 5383: 5372: 5370: 5361: 5355: 5354: 5347:nervous system 5342: 5341: 5334: 5327: 5319: 5310: 5309: 5306: 5305: 5294: 5274: 5269: 5268: 5266: 5265:Classification 5257: 5256: 5238: 5207:(9): a006387. 5187: 5144: 5101: 5052: 5008: 4981: 4970: 4910: 4881:(10): 2610–7. 4861: 4818: 4767: 4718: 4689:(2): 166–200. 4664: 4635:(2): 266–282. 4612: 4560: 4509: 4474: 4423: 4386:Genome Biology 4371: 4340:(12): 7425–9. 4320: 4269: 4238:(12): 7431–5. 4213: 4153: 4116:PLOS Pathogens 4102: 4100: 4099: 3981: 3932: 3883: 3876: 3858: 3804: 3778: 3753: 3727: 3692: 3636: 3607:(3): 161–178. 3576: 3548: 3499: 3462:(6): a020628. 3442: 3419:10.1038/nn1885 3393: 3370:10.1038/nn1876 3344: 3317:(4): 508–511. 3294: 3232: 3201:(6): 1464–77. 3181: 3125: 3113: 3091: 3064: 3015: 2954: 2909: 2894: 2871:10.1038/nn1988 2845: 2810: 2803: 2779: 2750:(5): 739–749. 2729: 2673: 2624: 2568: 2528: 2526:June 22, 2006. 2515: 2480: 2443:(5): 511–524. 2423: 2396:(11): 1984–9. 2380: 2345: 2302: 2253: 2209: 2158: 2143: 2123: 2096: 2062: 2055: 2037: 2023: 2001: 1931: 1863: 1852:. 17 July 2014 1837: 1786: 1757:(2): 204–219. 1737: 1686: 1641: 1616: 1565: 1510: 1509: 1507: 1504: 1503: 1502: 1497: 1492: 1487: 1480: 1477: 1444: 1441: 1414: 1411: 1406: 1403: 1365:is increased. 1343:covalent bonds 1251:transamidation 1243:covalent bonds 1221: 1218: 1207: 1204: 1191: 1188: 1169: 1168: 1150: 1131: 1128: 1115: 1112: 1075:Main article: 1072: 1069: 1015: 1012: 938: 935: 923: 920: 919: 918: 917: 916: 909: 905:macroautophagy 894:macroautophagy 882: 881: 880: 862: 861: 858: 855: 850:nucleus, e.g. 848: 836: 833: 831: 828: 827: 826: 819:prion diseases 809: 800: 773: 726:Stress granule 721: 718: 705: 702: 640: 637: 635: 632: 622:A study using 611: 608: 579: 576: 574: 571: 548:Main article: 545: 542: 522:Batten disease 517:Batten disease 515:Main article: 512: 511:Batten disease 509: 455:Main article: 452: 449: 445:HLA-DRB1*15:01 409:Main article: 406: 403: 330:Main article: 327: 324: 320:gut microbiome 259:Main article: 256: 253: 249:beta secretase 202:frontal cortex 167:Main article: 156: 153: 148: 145: 122:prion diseases 72: 71: 62: 56: 55: 43: 42: 34: 33: 25: 15: 9: 6: 4: 3: 2: 6940: 6929: 6926: 6924: 6921: 6919: 6916: 6914: 6911: 6910: 6908: 6893: 6892: 6883: 6881: 6880: 6871: 6870: 6867: 6861: 6858: 6856: 6853: 6851: 6848: 6846: 6843: 6841: 6838: 6836: 6833: 6831: 6828: 6826: 6823: 6821: 6818: 6816: 6813: 6811: 6808: 6806: 6803: 6801: 6798: 6796: 6793: 6791: 6788: 6786: 6783: 6781: 6778: 6776: 6773: 6771: 6768: 6767: 6765: 6761: 6755: 6752: 6750: 6747: 6745: 6744:Neurotheology 6742: 6740: 6739:Neurorobotics 6737: 6735: 6734:Neuropolitics 6732: 6730: 6727: 6725: 6722: 6720: 6717: 6715: 6712: 6710: 6707: 6705: 6702: 6700: 6699:Neuroethology 6697: 6695: 6692: 6690: 6687: 6685: 6682: 6680: 6677: 6675: 6672: 6670: 6667: 6665: 6662: 6660: 6657: 6655: 6652: 6650: 6647: 6645: 6642: 6640: 6637: 6635: 6632: 6631: 6629: 6623: 6617: 6614: 6612: 6609: 6607: 6604: 6602: 6599: 6597: 6596:Motor control 6594: 6592: 6589: 6587: 6586:Chronobiology 6584: 6582: 6579: 6577: 6574: 6573: 6571: 6569: 6563: 6557: 6554: 6552: 6549: 6547: 6546:Neurovirology 6544: 6542: 6539: 6537: 6534: 6532: 6529: 6527: 6524: 6522: 6519: 6517: 6514: 6512: 6509: 6507: 6504: 6502: 6499: 6497: 6494: 6492: 6489: 6487: 6484: 6482: 6479: 6477: 6474: 6472: 6469: 6467: 6464: 6462: 6459: 6457: 6454: 6452: 6449: 6448: 6446: 6444: 6438: 6433: 6423: 6420: 6418: 6415: 6413: 6410: 6408: 6405: 6403: 6400: 6398: 6395: 6393: 6392:Neurogenetics 6390: 6388: 6385: 6383: 6380: 6378: 6375: 6373: 6370: 6368: 6365: 6363: 6360: 6358: 6355: 6353: 6350: 6348: 6345: 6343: 6340: 6338: 6335: 6333: 6330: 6328: 6327:Brain-reading 6325: 6323: 6322:Brain mapping 6320: 6318: 6315: 6313: 6310: 6309: 6307: 6305: 6299: 6293: 6290: 6288: 6285: 6284: 6281: 6277: 6270: 6265: 6263: 6258: 6256: 6251: 6250: 6247: 6225: 6222: 6221: 6220: 6217: 6216: 6209: 6206: 6204: 6201: 6200: 6199: 6196: 6194: 6191: 6187: 6184: 6182: 6179: 6175: 6172: 6170: 6167: 6165: 6162: 6161: 6159: 6157: 6154: 6152: 6149: 6147: 6144: 6142: 6139: 6137: 6134: 6133: 6132: 6129: 6127: 6124: 6123: 6122: 6120: 6116: 6115: 6110: 6107: 6105: 6102: 6100: 6097: 6096: 6095: 6093: 6089: 6088: 6086: 6084: 6080: 6074: 6071: 6069: 6066: 6065: 6063: 6061: 6057: 6054: 6052: 6048: 6045: 6041: 6031: 6028: 6026: 6023: 6021: 6018: 6016: 6013: 6011: 6010:Reye syndrome 6008: 6006: 6003: 6002: 6000: 5996: 5990: 5987: 5985: 5982: 5978: 5975: 5973: 5970: 5968: 5965: 5963: 5962:Hydrocephalus 5960: 5959: 5958: 5955: 5954: 5952: 5950: 5946: 5934: 5930: 5929: 5928: 5925: 5924: 5922: 5918: 5912: 5908: 5906: 5903: 5901: 5898: 5897: 5895: 5893: 5889: 5883: 5879: 5877: 5874: 5872: 5869: 5867: 5864: 5863: 5861: 5859: 5855: 5849: 5845: 5843: 5840: 5838: 5835: 5833: 5830: 5829: 5827: 5825: 5821: 5817: 5814: 5812: 5806: 5800: 5796: 5794: 5791: 5789: 5786: 5784: 5781: 5780: 5778: 5776: 5775:Demyelinating 5772: 5762: 5759: 5758: 5756: 5754: 5750: 5744: 5741: 5740: 5739: 5738: 5732: 5729: 5727: 5724: 5720: 5717: 5716: 5715: 5711: 5708: 5704: 5701: 5697: 5694: 5693: 5692: 5689: 5688: 5687: 5684: 5683: 5681: 5679: 5675: 5669: 5666: 5664: 5663:Restless legs 5661: 5657: 5654: 5652: 5649: 5648: 5647: 5644: 5643: 5638: 5635: 5631: 5628: 5627: 5626: 5623: 5619: 5616: 5615: 5614: 5611: 5609: 5606: 5602: 5601:Blepharospasm 5599: 5597: 5594: 5592: 5589: 5587: 5584: 5583: 5582: 5579: 5578: 5577: 5574: 5573: 5568: 5565: 5563: 5560: 5558: 5557:Hemiballismus 5555: 5553: 5550: 5546: 5543: 5542: 5541: 5538: 5534: 5531: 5530: 5529: 5526: 5522: 5519: 5517: 5514: 5512: 5509: 5508: 5507: 5504: 5503: 5502: 5499: 5498: 5496: 5494: 5489: 5485: 5482: 5480: 5476: 5473: 5471: 5466: 5462: 5452: 5449: 5447: 5444: 5440: 5437: 5436: 5435: 5432: 5431: 5429: 5427: 5422: 5414: 5411: 5410: 5409: 5408:Brain abscess 5406: 5404: 5401: 5397: 5394: 5392: 5389: 5387: 5384: 5382: 5379: 5378: 5377: 5374: 5373: 5371: 5369: 5365: 5362: 5360: 5356: 5352: 5348: 5340: 5335: 5333: 5328: 5326: 5321: 5320: 5317: 5304: 5300: 5299: 5295: 5293: 5289: 5285: 5284: 5280: 5276: 5275: 5272: 5267: 5263: 5252: 5248: 5242: 5234: 5230: 5225: 5220: 5215: 5210: 5206: 5202: 5198: 5191: 5183: 5179: 5175: 5171: 5167: 5163: 5159: 5155: 5148: 5140: 5136: 5132: 5128: 5124: 5120: 5116: 5112: 5105: 5097: 5093: 5088: 5083: 5079: 5075: 5071: 5067: 5063: 5056: 5048: 5044: 5040: 5036: 5032: 5028: 5025:(5): 332–44. 5024: 5020: 5012: 5004: 5000: 4996: 4992: 4985: 4979: 4974: 4966: 4962: 4958: 4954: 4950: 4946: 4942: 4938: 4931: 4929: 4927: 4925: 4923: 4921: 4919: 4917: 4915: 4906: 4902: 4897: 4892: 4888: 4884: 4880: 4876: 4872: 4865: 4857: 4853: 4849: 4845: 4841: 4837: 4834:(5): 365–75. 4833: 4829: 4822: 4814: 4810: 4805: 4800: 4795: 4790: 4786: 4782: 4781:PLOS Genetics 4778: 4771: 4763: 4759: 4754: 4749: 4745: 4741: 4737: 4733: 4729: 4722: 4714: 4710: 4705: 4700: 4696: 4692: 4688: 4684: 4680: 4673: 4671: 4669: 4660: 4656: 4651: 4646: 4642: 4638: 4634: 4630: 4626: 4619: 4617: 4608: 4604: 4599: 4594: 4590: 4586: 4582: 4578: 4574: 4567: 4565: 4556: 4552: 4547: 4542: 4537: 4532: 4528: 4524: 4520: 4513: 4505: 4501: 4497: 4493: 4489: 4485: 4478: 4470: 4466: 4461: 4456: 4451: 4446: 4442: 4438: 4434: 4427: 4419: 4415: 4410: 4405: 4400: 4395: 4391: 4387: 4383: 4375: 4367: 4363: 4358: 4353: 4348: 4343: 4339: 4335: 4331: 4324: 4316: 4312: 4307: 4302: 4297: 4292: 4288: 4284: 4280: 4273: 4265: 4261: 4256: 4251: 4246: 4241: 4237: 4233: 4229: 4222: 4220: 4218: 4209: 4205: 4201: 4197: 4192: 4187: 4183: 4179: 4175: 4171: 4167: 4160: 4158: 4149: 4145: 4140: 4135: 4130: 4125: 4121: 4117: 4113: 4106: 4088: 4084: 4080: 4076: 4072: 4068: 4064: 4060: 4056: 4052: 4048: 4043: 4036: 4035: 4032: 4028: 4023: 4018: 4013: 4008: 4004: 4000: 3996: 3988: 3986: 3977: 3973: 3968: 3963: 3959: 3955: 3951: 3947: 3943: 3936: 3928: 3924: 3919: 3914: 3910: 3906: 3902: 3898: 3894: 3887: 3879: 3873: 3869: 3862: 3854: 3850: 3846: 3842: 3838: 3834: 3830: 3826: 3822: 3818: 3811: 3809: 3793: 3789: 3782: 3767: 3763: 3757: 3741: 3737: 3731: 3723: 3719: 3715: 3711: 3707: 3703: 3696: 3688: 3684: 3679: 3674: 3670: 3666: 3662: 3658: 3654: 3647: 3645: 3643: 3641: 3632: 3628: 3623: 3618: 3614: 3610: 3606: 3602: 3598: 3591: 3589: 3587: 3585: 3583: 3581: 3565: 3561: 3555: 3553: 3544: 3540: 3536: 3532: 3527: 3522: 3518: 3514: 3510: 3503: 3495: 3491: 3486: 3481: 3477: 3473: 3469: 3465: 3461: 3457: 3453: 3446: 3438: 3434: 3429: 3424: 3420: 3416: 3413:(5): 608–14. 3412: 3408: 3404: 3397: 3389: 3385: 3380: 3375: 3371: 3367: 3364:(5): 615–22. 3363: 3359: 3355: 3348: 3340: 3336: 3332: 3328: 3324: 3320: 3316: 3312: 3305: 3303: 3301: 3299: 3290: 3286: 3281: 3276: 3272: 3268: 3264: 3260: 3256: 3252: 3248: 3241: 3239: 3237: 3228: 3224: 3219: 3214: 3209: 3204: 3200: 3196: 3192: 3185: 3177: 3173: 3168: 3163: 3158: 3153: 3149: 3145: 3144:F1000Research 3141: 3134: 3132: 3130: 3116: 3110: 3106: 3102: 3095: 3081: 3077: 3071: 3069: 3060: 3056: 3051: 3046: 3042: 3038: 3035:(8): 378–85. 3034: 3030: 3026: 3019: 3011: 3007: 3002: 2997: 2993: 2989: 2985: 2981: 2977: 2973: 2969: 2961: 2959: 2950: 2946: 2941: 2936: 2932: 2928: 2924: 2920: 2913: 2907: 2903: 2898: 2890: 2886: 2881: 2876: 2872: 2868: 2864: 2860: 2856: 2849: 2841: 2837: 2833: 2829: 2826:(3): 265–76. 2825: 2821: 2814: 2806: 2800: 2796: 2795: 2790: 2783: 2775: 2771: 2766: 2761: 2757: 2753: 2749: 2745: 2741: 2733: 2725: 2721: 2716: 2711: 2706: 2701: 2697: 2693: 2689: 2682: 2680: 2678: 2669: 2665: 2660: 2655: 2651: 2647: 2643: 2639: 2635: 2628: 2620: 2616: 2611: 2606: 2601: 2596: 2592: 2588: 2584: 2577: 2575: 2573: 2564: 2560: 2556: 2552: 2548: 2544: 2537: 2535: 2533: 2525: 2519: 2511: 2507: 2503: 2499: 2495: 2491: 2484: 2476: 2472: 2468: 2464: 2459: 2454: 2450: 2446: 2442: 2438: 2434: 2427: 2419: 2415: 2411: 2407: 2403: 2399: 2395: 2391: 2384: 2376: 2372: 2368: 2364: 2360: 2356: 2349: 2341: 2337: 2333: 2329: 2325: 2321: 2317: 2313: 2306: 2298: 2294: 2289: 2284: 2280: 2276: 2272: 2268: 2264: 2257: 2249: 2245: 2240: 2235: 2231: 2227: 2223: 2216: 2214: 2205: 2201: 2196: 2191: 2186: 2181: 2177: 2173: 2169: 2162: 2154: 2150: 2146: 2140: 2136: 2135: 2127: 2119: 2115: 2111: 2107: 2100: 2092: 2088: 2084: 2080: 2076: 2072: 2066: 2058: 2052: 2048: 2041: 2026: 2020: 2013: 2012: 2005: 1997: 1993: 1988: 1983: 1979: 1975: 1971: 1967: 1963: 1959: 1955: 1948: 1946: 1944: 1942: 1940: 1938: 1936: 1927: 1923: 1919: 1915: 1911: 1907: 1903: 1899: 1895: 1891: 1884: 1882: 1880: 1878: 1876: 1874: 1872: 1870: 1868: 1851: 1850:JPND Research 1847: 1841: 1833: 1829: 1824: 1819: 1814: 1809: 1805: 1801: 1797: 1790: 1782: 1778: 1773: 1768: 1764: 1760: 1756: 1752: 1748: 1741: 1733: 1729: 1724: 1719: 1714: 1709: 1705: 1701: 1697: 1690: 1682: 1678: 1673: 1668: 1664: 1660: 1656: 1652: 1645: 1630: 1626: 1620: 1612: 1608: 1603: 1598: 1593: 1588: 1584: 1580: 1579:Int J Mol Sci 1576: 1569: 1561: 1557: 1552: 1547: 1543: 1539: 1535: 1531: 1530: 1525: 1518: 1516: 1511: 1501: 1498: 1496: 1493: 1491: 1490:JUNQ and IPOD 1488: 1486: 1483: 1482: 1476: 1474: 1470: 1466: 1461: 1457: 1454: 1453:immunotherapy 1449: 1440: 1438: 1432: 1429: 1424: 1423:animal models 1420: 1410: 1402: 1400: 1396: 1392: 1388: 1386: 1382: 1378: 1374: 1372: 1366: 1364: 1361: 1357: 1353: 1351: 1346: 1344: 1340: 1336: 1332: 1328: 1324: 1320: 1316: 1313: 1311: 1308: 1303: 1301: 1297: 1293: 1289: 1285: 1281: 1277: 1272: 1270: 1265: 1263: 1258: 1256: 1252: 1248: 1244: 1240: 1235: 1233: 1230: 1226: 1217: 1214: 1203: 1201: 1200:autophagosome 1197: 1187: 1185: 1181: 1177: 1173: 1166: 1162: 1158: 1154: 1151: 1148: 1144: 1141: 1140: 1139: 1136: 1127: 1124: 1120: 1111: 1109: 1105: 1101: 1097: 1093: 1089: 1084: 1078: 1068: 1066: 1062: 1058: 1054: 1050: 1046: 1042: 1038: 1033: 1029: 1025: 1021: 1011: 1009: 1005: 1004:transcription 1001: 997: 993: 991: 987: 983: 979: 974: 972: 968: 964: 960: 956: 952: 948: 944: 934: 933: 930: 913: 910: 906: 903: 902: 900: 896: 895: 890: 886: 883: 878: 877: 874: 870: 867: 866: 865: 859: 856: 853: 849: 846: 845: 844: 842: 841:proteopathies 824: 820: 816: 814: 810: 807: 805: 801: 798: 794: 790: 786: 783: 780: 778: 774: 771: 767: 763: 759: 755: 751: 749: 745: 744: 743: 741: 737: 733: 732:proteopathies 727: 717: 715: 714:Braak staging 711: 701: 699: 695: 690: 688: 684: 680: 676: 670: 668: 664: 660: 656: 650: 646: 631: 629: 625: 616: 607: 604: 599: 595: 591: 585: 570: 568: 564: 560: 556: 551: 541: 539: 535: 531: 527: 523: 518: 508: 506: 505:motor neurons 502: 498: 493: 491: 487: 483: 479: 475: 471: 467: 463: 458: 448: 446: 441: 437: 433: 429: 425: 421: 417: 412: 402: 400: 396: 392: 388: 383: 381: 377: 373: 369: 365: 361: 357: 353: 349: 346: 342: 338: 333: 323: 321: 317: 313: 309: 304: 302: 298: 294: 290: 286: 282: 278: 273: 271: 267: 262: 252: 250: 246: 242: 238: 234: 230: 226: 222: 218: 214: 209: 207: 203: 199: 198:parietal lobe 195: 194:temporal lobe 191: 187: 183: 179: 175: 170: 161: 152: 144: 142: 137: 135: 131: 130:proteinopathy 127: 123: 119: 115: 111: 107: 103: 99: 95: 91: 87: 83: 79: 70: 66: 63: 61: 57: 53: 49: 44: 40: 35: 30: 22: 6889: 6877: 6825:Neuroimaging 6820:Neurogenesis 6804: 6704:Neurohistory 6669:Neurobiotics 6568:neuroscience 6536:Neurosurgery 6461:Epileptology 6443:neuroscience 6412:Neurophysics 6402:Neurometrics 6377:Neurobiology 6372:Neuroanatomy 6342:Connectomics 6276:Neuroscience 6218: 6117: 6090: 6051:Degenerative 6050: 5788:Inflammatory 5735: 5668:Stiff-person 5506:Parkinsonism 5479:Degenerative 5478: 5376:Encephalitis 5359:Inflammation 5349:, primarily 5296: 5277: 5241: 5204: 5200: 5190: 5157: 5153: 5147: 5117:(4): 642–9. 5114: 5110: 5104: 5069: 5065: 5055: 5022: 5018: 5011: 4997:(2): 113–5. 4994: 4990: 4984: 4973: 4943:(2): 653–8. 4940: 4936: 4878: 4874: 4864: 4831: 4827: 4821: 4787:(10): e135. 4784: 4780: 4770: 4735: 4731: 4721: 4686: 4682: 4632: 4628: 4580: 4576: 4526: 4522: 4512: 4487: 4483: 4477: 4440: 4436: 4426: 4389: 4385: 4374: 4337: 4333: 4323: 4289:(12): 7405. 4286: 4282: 4272: 4235: 4231: 4173: 4169: 4119: 4115: 4105: 4091:. Retrieved 4050: 4046: 4002: 3998: 3949: 3945: 3935: 3900: 3896: 3886: 3867: 3861: 3820: 3816: 3795:. Retrieved 3791: 3781: 3769:. Retrieved 3765: 3756: 3744:. Retrieved 3739: 3730: 3705: 3701: 3695: 3660: 3656: 3604: 3600: 3567:. Retrieved 3563: 3519:(5): 535–7. 3516: 3512: 3502: 3459: 3455: 3445: 3410: 3406: 3396: 3361: 3357: 3347: 3314: 3310: 3257:(1): 15661. 3254: 3250: 3198: 3194: 3184: 3147: 3143: 3118:, retrieved 3104: 3094: 3083:. Retrieved 3079: 3032: 3028: 3018: 2975: 2971: 2922: 2912: 2897: 2862: 2858: 2848: 2823: 2819: 2813: 2794:Neuroscience 2793: 2782: 2747: 2743: 2732: 2695: 2691: 2641: 2637: 2627: 2590: 2586: 2546: 2542: 2518: 2496:(1): 14–26. 2493: 2489: 2483: 2440: 2436: 2426: 2393: 2389: 2383: 2358: 2354: 2348: 2315: 2311: 2305: 2270: 2266: 2256: 2229: 2225: 2175: 2171: 2161: 2133: 2126: 2109: 2105: 2099: 2077:. Springer. 2074: 2065: 2046: 2040: 2028:. Retrieved 2010: 2004: 1961: 1957: 1893: 1889: 1854:. Retrieved 1849: 1840: 1803: 1799: 1789: 1754: 1750: 1740: 1706:(11): 1845. 1703: 1700:Antioxidants 1699: 1689: 1654: 1644: 1632:. Retrieved 1628: 1619: 1582: 1578: 1568: 1533: 1527: 1469:table tennis 1462: 1458: 1451:The goal of 1450: 1446: 1437:amyloid-beta 1433: 1416: 1408: 1390: 1389: 1369:Presence of 1368: 1367: 1348: 1347: 1315:Amyloid-beta 1305: 1304: 1296:Huntington's 1280:amyloid-beta 1278:, these are 1273: 1266: 1259: 1255:crosslinking 1236: 1232:ubiquitously 1223: 1209: 1196:phagocytosis 1193: 1183: 1179: 1170: 1157:cytochrome c 1152: 1142: 1133: 1117: 1104:mitochondria 1100:microtubules 1080: 1017: 994: 986:Huntington's 975: 943:cytochrome c 940: 925: 911: 904: 898: 892: 884: 868: 863: 838: 811: 804:amyloid beta 802: 775: 746: 729: 707: 691: 686: 682: 671: 652: 621: 587: 573:Risk factors 553: 520: 496: 494: 466:Lou Gehrig's 460: 444: 414: 384: 356:astrogliosis 347: 335: 305: 277:dopaminergic 274: 270:bradykinesia 264: 225:amyloid beta 210: 172: 150: 138: 85: 77: 75: 6694:Neuroethics 6541:Neurotology 6203:Fazio–Londe 6043:Both/either 5837:Generalised 5696:Early-onset 5691:Alzheimer's 5426:spinal cord 4937:Amino Acids 4529:: 2525967. 4093:15 February 3766:Mayo Clinic 3569:30 November 2902:Purves 2001 2807:. NBK10847. 2318:(1): 1–32. 2178:: 631–653. 1856:February 7, 1806:(8): 1583. 1585:(3): 1851. 1397:with these 1288:Parkinson's 1008:antioxidant 982:Parkinson's 978:Alzheimer's 915:substrates. 793:Pick bodies 785:tau protein 754:Lewy bodies 736:aggregation 704:Epigenetics 596:as well as 584:Aging brain 557:(CJD) is a 472:(UMNs) and 440:macrophages 316:tau protein 314:(GBA), and 297:Lewy bodies 134:therapeutic 126:subcellular 118:tauopathies 6923:Senescence 6907:Categories 6855:Neurotoxin 6556:Psychiatry 5811:paroxysmal 5783:Autoimmune 5576:Dyskinesia 5446:Meningitis 5424:Brain and 5072:: 175–93. 4738:: 245–67. 4490:: 91–123. 3120:2020-12-07 3085:2020-11-30 2549:: 151–73. 2030:14 October 1751:Immunology 1506:References 1405:Management 1356:expression 1331:substrates 1327:huntingtin 1310:substrates 1300:huntingtin 1227:are human 1180:initiators 1176:amino acid 1149:-8 or -10. 1024:DNA damage 1014:DNA damage 887:a form of 724:See also: 687:Drosophila 683:C. elegans 643:See also: 634:Mechanisms 628:UK Biobank 610:Infections 603:DNA damage 501:astrocytes 69:Psychiatry 6800:Neurochip 6566:Cognitive 6491:Neurology 5808:Episodic/ 5686:Tauopathy 5637:Akathisia 5625:Myoclonus 5608:Athetosis 5540:Tauopathy 4991:Pharm Med 4392:(1): 90. 4208:205037169 4083:256193462 3722:241832253 3708:(5): 22. 3657:Neurology 3476:1943-0264 3339:208186566 3203:CiteSeerX 2390:Neurology 2153:859536969 2091:1559-0283 1800:Molecules 1536:(4): 20. 1184:effectors 1135:Apoptosis 1010:defense. 945:from the 873:ubiquitin 795:found in 659:glutamine 528:known as 310:(LRRK2), 293:ubiquitin 231:(APP), a 65:Neurology 60:Specialty 6879:Category 6763:Concepts 6709:Neurolaw 6441:Clinical 6174:SMALED2B 6169:SMALED2A 5866:Migraine 5858:Headache 5824:epilepsy 5820:Seizures 5678:Dementia 5581:Dystonia 5251:Fox News 5233:22951439 5139:54334969 5131:15080893 5096:18352830 5047:39817779 5039:18790460 4965:19739739 4957:19960212 4905:16200193 4856:33018251 4848:12728264 4813:17069462 4762:20345246 4713:21550379 4659:25033177 4607:27663141 4555:28785371 4504:18333761 4469:29947927 4418:33771206 4366:18957430 4315:18957428 4264:18957429 4200:18401401 4148:35925897 4087:Archived 4075:36690772 4031:36669485 4022:10079561 3976:28438892 3927:26385091 3845:17051205 3797:31 March 3771:31 March 3746:31 March 3687:32300063 3631:30783219 3535:17453052 3494:25877220 3437:17435754 3388:17435755 3331:31743477 3289:32973334 3227:18490361 3176:31885862 3150:: 2100. 3059:23768628 3010:32675289 2949:10923984 2889:17965655 2840:18279698 2774:28195358 2724:33274040 2668:26601739 2619:20693280 2563:18558852 2510:26718594 2475:25739126 2467:15004691 2458:11138910 2418:25017332 2410:15184601 2375:15787600 2340:25376584 2332:12927332 2297:16822978 2248:54359937 2204:34093032 2118:12934968 1996:17051206 1918:17051204 1832:31013638 1781:29513402 1732:34829716 1681:38585882 1672:10996678 1611:35163773 1560:28716886 1479:See also 1213:necrosis 1172:Caspases 1147:caspases 871:protein 696:and the 679:nematode 639:Genetics 538:dementia 534:epilepsy 497:in vitro 368:temporal 360:striatum 285:midbrain 243:such as 221:peptides 182:synapses 141:dementia 6891:Commons 6304:science 6292:History 6287:Outline 6186:SMA-PME 6181:SMA-PCH 6164:SMALED1 5876:Tension 5871:Cluster 5596:Meige's 5413:Amoebic 5303:D019636 5224:3426815 5182:2111583 5162:Bibcode 5154:Science 5087:2561172 4896:1236695 4804:1626106 4753:5223592 4704:3123739 4650:5564444 4598:5316312 4546:5529664 4460:6063327 4409:8004462 4357:2658037 4306:2658033 4255:2658038 4178:Bibcode 4139:9352104 4055:Bibcode 3967:5452017 3918:4588127 3853:4421515 3825:Bibcode 3678:7455368 3622:6681450 3543:2987257 3485:4448607 3428:3139463 3379:3799799 3280:7518279 3259:Bibcode 3167:6915812 3050:3955166 3001:7859879 2980:Bibcode 2972:Science 2940:1468094 2880:3110080 2765:5469442 2715:7683170 2698:: 1–5. 2659:4688052 2610:2952250 2288:6673945 2195:8169052 1987:3970704 1966:Bibcode 1926:4411895 1898:Bibcode 1823:6514564 1772:5980185 1723:8614795 1655:bioRxiv 1634:12 July 1602:8837071 1551:5880171 1485:Amyloid 1428:Dimebon 1358:of the 1262:binding 1245:termed 1229:enzymes 1161:nucleus 1092:kinesin 1026:in the 996:Neurons 606:speed. 490:C9orf72 422:of the 364:frontal 241:enzymes 237:cleaved 192:of the 190:atrophy 184:in the 178:neurons 82:neurons 46:Normal 6627:fields 5905:Stroke 5719:Pick's 5646:Tremor 5613:Chorea 5231: 5221: 5180: 5137: 5129: 5094: 5084: 5045: 5037: 4963: 4955: 4903: 4893: 4854: 4846: 4811: 4801: 4760: 4750: 4711: 4701: 4657: 4647: 4629:Neuron 4605: 4595: 4553: 4543: 4502: 4467: 4457: 4416: 4406: 4364: 4354: 4313: 4303: 4262: 4252: 4206: 4198: 4170:Nature 4146: 4136: 4081: 4073: 4047:Nature 4029: 4019: 3999:Neuron 3974: 3964: 3925: 3915: 3874: 3851: 3843: 3817:Nature 3720: 3685: 3675: 3629: 3619: 3541: 3533: 3492: 3482: 3474: 3435: 3425: 3386: 3376: 3337: 3329: 3287: 3277: 3225: 3205: 3174: 3164: 3111: 3057: 3047: 3008: 2998: 2947: 2937: 2887: 2877: 2838: 2801: 2772: 2762: 2722: 2712: 2666: 2656: 2617: 2607: 2561: 2508: 2473: 2465: 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