Aggregates 1997 alpha synuclein lewy bodies. Medical search. Frequent questions

There are at different types of dementias with different but inter-related causes and symptoms [ 1 ], the most prevalent of which is Alzheimer's disease followed by vascular dementia, dementia with Lewy bodies and frontotemporal dementia. (iospress.com)
MSA is characterized by the following, which can be present in any combination: autonomic dysfunction parkinsonism (muscle rigidity +/ tremor and slow movement) cerebellar ataxia (Poor coordination/unsteady walking, double vision) A variant with combined features of MSA and dementia with Lewy bodies may also exist. (wikipedia.org)
Lewy bodies are observed in several diseases (Parkinson's disease, dementia with Lewy bodies, incidental Lewy Body disease ( Wakabayashi et al, 2012 )) but are not found in healthy cells and are related to the aggresome, a structure found in cells that are processing large amounts of waste, unfolded polypeptide ( Johnston et al, 1998 ). (biorxiv.org)
For example, Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA) are characterized by accumulation of misfolded α-synuclein in neuronal and/or glial cells, and therefore these diseases are termed α-synucleinopathies. (elifesciences.org)
Moreover, the accumulation of aSyn in Lewy Bodies and Lewy neurites in disorders such as PD, dementia with Lewy bodies, or multiple system atrophy, suggests aSyn misfolding and aggregation plays an important role in these disorders, collectively known as synucleinopathies. (biomedcentral.com)
The purpose of this review is to aid primary care providers in distinguishing dementia with Lewy bodies (DLB) from Alzheimer's disease and from Parkinson's disease with dementia. (psychiatrist.com)
A PubMed search was undertaken using the keywords Lewy body dementia, dementia with Lewy bodies, and Lewy body disease. (psychiatrist.com)
Dementia with Lewy bodies is the second leading cause of dementia after Alzheimer's disease. (psychiatrist.com)
Dementia with Lewy bodies is an often missed diagnosis. (psychiatrist.com)
D ementia with Lewy bodies (DLB) accounts for 15% to 35% of dementia cases. (psychiatrist.com)
Cholinesterase inhibitors are the first-line treatment for dementia with Lewy bodies. (psychiatrist.com)
Atypical Parkinsonism affects about five to ten percent of patients with Parkinsonism and includes the diseases Corticobasal Degeneration, Progressive Supranuclear Palsy, Lewy Body Dementia and Multiple System Atrophy. (bz-bx.net)
Atypical Parkinsonian syndromes (APS) feature a heterogeneous group of progressive neurodegenerative diseases, to which multiple system atrophy (MSA), dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are counted. (bz-bx.net)

These mutations cause α-syn to form oligomers and fibrils then aggregates. (biorxiv.org)
Since the fibrils and precursor oligomers of alpha-synuclein are cytotoxic to the neuron, inhibitors that prevent the formation of oligomers and/or fibrils might open the way to a novel therapeutic approach to PD. (biomedcentral.com)
Several in vitro studies have shown the propensity of α-Syn to aggregate into amyloid fibrils, a process that is accelerated by the truncation of its C-terminal. (biomedcentral.com)
In the current study, Lasmézas and her team looked at cell cultures of neurons that were induced to accumulate fibrils made of misfolded α-synuclein, mimicking Lewy bodies in patients with Parkinson's. (drugdiscoverynews.com)
Sometimes the nerve cells can efficiently degrade the α-synuclein fibrils, but if they get overwhelmed, the degradation may be incomplete," noted Lasmézas. (drugdiscoverynews.com)
Lasmézas pointed out that these findings also have implications for designing treatments for Parkinson's, noting that some drugs currently under development are focused on getting rid of larger fibrils that make up Lewy bodies. (drugdiscoverynews.com)
Here, we generated two types of α-synuclein fibrils from identical monomer and investigated their seeding and propagation ability in mice and primary-cultured neurons. (elifesciences.org)
These synthetic α-synuclein fibrils can act as seeds and induce seeded aggregation of α-synuclein in cultured cells or primary cultured neurons, as well as in animal brains. (elifesciences.org)
This aggregation may lead to developing Lewy bodies, fibrils, plaques and tangles inside neurons that trigger apoptosis. (springeropen.com)
Cellular processing of α-synuclein fibrils results in distinct physiological C-terminal truncations with a major cleavage site at residue Glu 114. (neurotree.org)
In Parkinson's disease, insoluble α-synuclein fibrils compose the Lewy bodies and Lewy neurites. (encyclopedia.pub)

PD and other neurodegenerative disorders, such as demential with Lewy bodies, and multiple system atrophy, are also characterized by the accumulation of aggregated alpha-synuclein (aSyn) in proteinaceous inclusions known as Lewy bodies (LBs) or Lewy neurites [ 54 ]. (biomedcentral.com)
The 2 major neuropathologic findings in Parkinson disease are loss of pigmented dopaminergic neurons of the substantia nigra pars compacta and the presence of Lewy bodies and Lewy neurites. (medscape.com)
Micrograph of immunostained α-synuclein (brown) in Lewy bodies (large clumps) and Lewy neurites (thread-like structures) in the cerebral cortex of a patient with Lewy body disease , a synucleinopathy . (wikipedia.org)
Lewy neurites are atypical neurites made up of α-synuclein filaments and granular material [ 4 ] . (encyclopedia.pub)
These Lewy neurites pile up in the amygdala and striatum of Parkinsonian patients [ 4 ] . (encyclopedia.pub)
Lewy neurites can restrain neuronal transport and, thus, compromise neuronal activity and survival. (encyclopedia.pub)

In this study, we first characterized the aggregation and cytotoxicity of C-truncated alpha-synuclein119 and alpha-synuclein133 which have been found in both the normal and the pathogenic brain. (biomedcentral.com)
Although both of alpha-synuclein119 and alpha-synuclein133 showed a high cytotoxicity, alpha-synuclein133 showed a similar aggregation with full-length alpha-synuclein and no acceleration effect. (biomedcentral.com)
Abnormal α-synuclein aggregation has been implicated in several diseases and is known to spread in a prion-like manner. (elifesciences.org)
Several lines of evidence suggest that phosphorylation of α-synuclein (α-syn) at S87 or S129 may play an important role in regulating its aggregation, fibrillogenesis, Lewy body formation, and neurotoxicity in vivo . (jneurosci.org)
Aggregation of the protein alpha-synuclein is found in Lewy bodies, a pathological hallmark of Parkinson's disease. (michaeljfox.org)
The results obtained are fundamentally important not only for understanding the development of the pathological process in α-synucleinopathies, but which is more important, for the development of new therapeutic approaches that will stop the extension of the human α-synuclein aggregation pathology throughout the nervous system, and the validation of these approaches in preclinical trials. (eco-vector.com)
In Parkinson's and Alzheimer's disease, protein aggregation concerns α-synuclein, Tau and β-amyloid proteins, respectively, although β-amyloid proteins are equally present in Parkinson's disease. (encyclopedia.pub)
Nora Bengoa-Vergniory's research focuses on alpha-synuclein aggregation and neuroinflammation in neurodegeneration, specifically in Parkinson's and Alzheimer's diseases. (wavebreaktx.com)
Dr. Bengoa-Vergniory joined the Wade-Martins laboratory at Oxford University in 2015 for her postdoctoral training on the role of alpha-synuclein aggregation in Parkinson's disease. (wavebreaktx.com)
In 2018, she became an Oxford-BMS/Celgene Research Fellow studying alpha-synuclein aggregation and glial activation in Parkinson's. (wavebreaktx.com)

Within neurons of Parkinson's disease patients, large alpha-synuclein-positive intracellular inclusions known as Lewy bodies are observed ( Wakabayashi et al, 2012 ). (biorxiv.org)
PD etiology is also linked to the presence of cellular inclusions, known as Lewy bodies (LBs), which have been identified as postmortem hallmarks of PD [ 4 , 5 ]. (hindawi.com)

Synucleins are a family of soluble proteins common to vertebrates, primarily expressed in neural tissue and in certain tumors. (wikipedia.org)
The synuclein family includes three known proteins: alpha-synuclein, beta-synuclein, and gamma-synuclein. (wikipedia.org)
Synuclein family members are not found outside vertebrates, although they have some conserved structural similarity with plant 'late-embryo-abundant' proteins. (wikipedia.org)
Alpha-synuclein InterPro: IPR002460 Beta-synuclein InterPro: IPR002461 Gamma-synuclein InterPro: IPR002462 Normal cellular functions have not been determined for any of the synuclein proteins. (wikipedia.org)
The aggresome is juxtanuclear inclusion body containing heat-shock proteins and components of the ubiquitin-proteasome system ( Olzmann et al, 2008 ). (biorxiv.org)
Copper ions bind to biomolecules (e.g., peptides and proteins) playing an essential role in many biological and physiological pathways in the human body. (mdpi.com)
In simulations, elevations in the aggregations of major proteins involved in the pathology of AD and PD including amyloid beta, alpha synuclein, tau have been modelled. (springeropen.com)
A clumping of proteins inside cell bodies in the brain, which may be toxic. (michaeljfox.org)
On the path to achieving this, we have developed SAIT, a novel therapy that stimulates the body to find and fight proteins that are central to the development and progression of these diseases. (affiris.com)
proteinopathic adj ), or proteopathy , protein conformational disorder , or protein misfolding disease , is a class of diseases in which certain proteins become structurally abnormal, and thereby disrupt the function of cells , tissues and organs of the body. (wikipedia.org)
[10] Furthermore, evidence has emerged that small, non-fibrillar protein aggregates known as oligomers are toxic to the cells of an affected organ, and that amyloidogenic proteins in their fibrillar form may be relatively benign. (wikipedia.org)
For example, cystic fibrosis is caused by a defective cystic fibrosis transmembrane conductance regulator (CFTR) protein, [3] and in amyotrophic lateral sclerosis / frontotemporal lobar degeneration (FTLD), certain gene-regulating proteins inappropriately aggregate in the cytoplasm, and thus are unable to perform their normal tasks within the nucleus. (wikipedia.org)
Although they differ in their neuropathology, they have, as a common correlate, cellular inclusion bodies of misfolded proteins that lead to cell degeneration in the corresponding brain areas. (bz-bx.net)
One of the first known mechanisms is the accumulation of proteins: α-synuclein (Parkinson's disease), Tau (Alzheimer's disease) and β-amyloid (Alzheimer's disease and Parkinson's disease) proteins. (encyclopedia.pub)
Hsp70, Hsp90, and their co-chaperones are crucial members of the proteostasis network that are able to recognize misfolded proteins, aberrant condensates and protein aggregates, triaging proteins for refolding or degradation. (encyclopedia.pub)

The major filamentous component of Papp-Lantos bodies, glial and neuronal cytoplasmic inclusions, is alpha-synuclein. (wikipedia.org)
Recently, it has been shown that not only full-length alpha-synuclein, but also C-terminal truncated forms exist in the normal brain, as well as Lewy bodies, which are cytoplasmic inclusions in PD. (biomedcentral.com)
Due to the underlying pathology, alpha-synuclein deposits in oligodentroglia (glial cytoplasmic inclusions, GCI) of the affected areas in the brain with subsequent cell death, MSA is an α-synucleinopathy. (bz-bx.net)

The central hypothesis for the cellular mechanism of Parkinson's disease is the toxic accumulation of alpha-synuclein, dysfunctional protein clearance and oxidative stress collectively leading to the degeneration of dopaminergic neurons. (michaeljfox.org)
The absence of inclusions could be due to highly active autophagy that prevents the accumulation of exogenous alpha-synuclein. (michaeljfox.org)
The researchers found that loss of autophagy caused accumulation of alpha-synuclein protein in the brain. (michaeljfox.org)
Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the progressive accumulation in selected neurons of protein inclusions containing alpha-synuclein and ubiquitin (5, 6). (signalchem.com)
Parkinson's disease (PD) involves the selective damage of dopaminergic neuron cells resulting from the accumulation and fibril formation of alpha-synuclein. (biomedcentral.com)
One α-synuclein fibril induced marked accumulation of phosphorylated α-synuclein and ubiquitinated protein aggregates, while the other did not, indicating the formation of α-synuclein two strains. (elifesciences.org)
Both are also characterised by an accumulation of protein aggregates resulting in progressive neuronal loss, suggesting a common underlying pathology. (ukessays.com)
5 One proposed mechanism is α-synuclein-induced impairment of the ubiquitin-proteasomal system (UPS), resulting in protein accumulation and leading to cell degeneration. (touchneurology.com)

The triggers for the pathologic amyloid transformation of alpha-synuclein remain unknown. (techscience.com)
SNCA fibrillar aggregates represent the major non A-beta component of Alzheimers disease amyloid plaque, and a major component of Lewy body inclusions, and Parkinson's disease. (signalchem.com)
Our results demonstrate that PQQ inhibits the amyloid fibril formation and cytotoxicity of the C-truncated alpha-synuclein variants. (biomedcentral.com)
AD is characterized diagnostically by two histologic findings: (1) extracellular amorphus eosinophilic deposits of amyloid consisting of Aβ peptides (a cleavage product of amyloid precursor protein [APP]), which are referred to as amyloid plaques, and (2) intraneuronal aggregates of abnormally modified microtubule-associated protein tau (neurofibrillary tangles) (see the image below). (medscape.com)

The neuropathologic hallmark of Parkinson's disease is the presence of brain intraneuronal aggregates of misfolded alpha-synuclein, known as Lewy bodies. (techscience.com)

1 This is consistent with the Braak hypothesis suggesting that PD patients have Lewy body pathology in autonomic centres and nerves that include the dorsal motor nucleus of the glossopharyngeal and vagal nerves, gastrointestinal submucosal plexus and postganglionic sympathetic nervous system, which is present in the pre-motor stage before nigral involvement. (bmj.com)

Current pre-clinical models with overexpression of human mutant alpha-synuclein do not display Lewy body-like inclusions in dopamine neurons. (michaeljfox.org)

In an AAV-synuclein mouse model of PD, we have found that over-abundance of α-SYN triggers the expression of NF-κB p65, and leads to microglial activation and DA neurodegeneration. (biomedcentral.com)
In this study, a computational model of AD and PD have been modelled using biochemical systems theory, and shows how Tumour Necrosis Factor alpha (TNF훼) regulated neuroinflammation, oxidative stress and insulin pathways can dysregulate its downstream signalling cascade that lead to neurodegeneration observed in AD and PD. (springeropen.com)
Targeted proteolytic products of τ and α-synuclein in neurodegeneration. (neurotree.org)

The pathologic hallmark of PD is the presence of intracytoplasmic eosinophyllic, proteinaceous inclusions, termed Lewy bodies (LB), in surviving neurons. (touchneurology.com)

Alpha-synuclein (α-Syn), the primary pathological marker of PD, can gather in the SN and trigger a neuroinflammatory response by activating microglia which can further activate the dopaminergic neuron's neuroimmune response mediated by reactive T cells through antigen presentation. (biomedcentral.com)
An approach to obtaining clones of mouse genetically modified stem cells expressing pathological humanized α-synuclein, has been proposed and implemented. (eco-vector.com)
Parkinson's disease (PD) is a common neurodegenerative disorder that exhibits motor and non-motor symptoms, as well as pathological hallmarks, including dopaminergic (DA) neuron death and formation of alpha-synuclein (alpha-Syn) Lewy bodies. (sdbonline.org)

Strikingly, overexpression of the phosphomimic mutant S87E did not show any toxic effect on dopaminergic neurons and resulted in significantly less α-syn aggregates, dystrophic fibers, and motor impairment. (jneurosci.org)
The etiology of Parkinson's disease (PD) is linked with cellular inclusions in the substantia nigra pars compacta region of the brain that are enriched in the misfolded presynaptic protein α -synuclein ( α S) and death of the dopaminergic neurons. (hindawi.com)
The major constituent of LBs is aggregated α -synuclein ( α S), an intrinsically unfolded protein predominantly localized in the presynaptic regions of dopaminergic neurons. (hindawi.com)
Lewy bodies are existent in the dopaminergic neurons of substantia nigra pars compacta. (encyclopedia.pub)

The protein alpha-synuclein (α-SYN), which is found in the Lewy bodies of dopamine-producing (DA) neurons in the substantia nigra (SN), has an important role in the pathogenesis of Parkinson's disease (PD). (biomedcentral.com)
Carboxyl truncation of α-synuclein occurs early and is influenced by human APOE genotype in transgenic mouse models of α-synuclein pathogenesis. (neurotree.org)
α-synuclein is one of the key molecular links in the pathogenesis of Parkinson's disease. (eco-vector.com)
It is unclear whether these aggregates contribute to the pathogenesis, are a simple by-product or even part of an attempted protective mechanism, described as the aggresome theory (McNaught et al. (ukessays.com)

α-synuclein (aSyn) is associated with both sporadic and familial forms of Parkinson's disease (PD), the second most common neurodegenerative disorder after Alzheimer's disease. (biomedcentral.com)

These Lewy bodies are round intraneuronal and positive round inclusions of α-synuclein and ubiquitin [ 3 ] . (encyclopedia.pub)

α-Synuclein (140 aa) is a natively unfolded protein that is enriched in the presynaptic terminal of the neurons in the brain. (biomedcentral.com)
α-Synuclein is a natively unfolded protein of 140 amino acid residues, normally found in both soluble and membrane-associated fractions and localized in synaptic termini. (elifesciences.org)

In addition, the mutant dopamine neurons develop ubiquitinated, p62-positive inclusions throughout the cell bodies and dendrites of the substantia nigra in models. (michaeljfox.org)
Histological brain sections of PD patients shows characteristic, large inclusion bodies in the cytosol of surviving neurons of the substantia nigra, as well as locus ceruleus and surrounding brainstem nuclei, called Lewy bodies (Kumar et al. (ukessays.com)
However, Lewy bodies are not found in some cases of juvenile onset PD, which suggests that the inclusions are not crucial for neuronal death in the substantia nigra (Fahn & Salzer 2004). (ukessays.com)

Protein aggregates are the pathogenic hallmarks of many different neurodegenerative diseases and include the Lewy bodies found in Parkinson's disease. (biorxiv.org)
There are two hallmarks of the disease: a die-off of the brain cells that produce dopamine and protein clumps called Lewy bodies inside the neurons. (drugdiscoverynews.com)

2005). These are aggregates of ï ¡-synuclein (Spillantini et al. (ukessays.com)

Alpha-Synuclein (SNCA) is expressed predominantly in the brain, where it is concentrated in presynaptic nerve terminals (1). (signalchem.com)
Disease-linked missense mutations and multiplication of the SNCA gene encoding α-synuclein have been reported in familial forms of α-synucleinopathies, indicating that structural changes and overexpression of α-synuclein protein are involved in the development of α-synucleinopathies ( Wong and Krainc, 2017 ). (elifesciences.org)
The accumulated data indicate that pathogenic mutations in the Snca gene are associated with the development of neurodegenerative brain damage, indicating the relevance of studying the synuclein neurobiological role. (eco-vector.com)
As a result of the study, a strategy for CRISPR/Cas9-assisted homologous recombination in the genome of mouse embryonic stem cells has been developed to create a fully humanized Snca gene encoding α-synuclein, and the clone genome of mouse embryonic stem cells has been edited using a CRISPR technology. (eco-vector.com)

Alpha synuclein in neurodegenerative disorders: murderer or accomplice? (wikipedia.org)

Autophagy is a regulated lysosomal degradation which has the capacity to clear large protein/lipid complexes, toxic aggregates and cellular organelles. (michaeljfox.org)

This mutation has been linked to early-onset Parkinson's Disease (7) and increased rates of alpha synuclein fibrillization (8). (signalchem.com)

Downregulating aux expression leads to progressive loss of climbing ability , decreased lifespan , and age-dependent DA neuron death similar to alpha-Syn overexpression. (sdbonline.org)

Lewy bodies are also found in low numbers in normal aging and AD (Jellinger 2001). (ukessays.com)
Animal models of the disease, created using neurotoxins such as rotenone or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), or transgenic mice that overexpress human SYN gene (for ï ¡-synuclein) mutations, do not faithfully replicate the structure and antigenicity of the Lewy bodies found in PD (Dickson 2001). (ukessays.com)

Optical pulse labeling studies reveal exogenous seeding slows α-synuclein clearance. (neurotree.org)

It is unclear if these aggregates or Lewy bodies are a means to protect the cell from smaller unfolded units of α-syn or if these structures cause neuronal death by obstructing the normal function of the cell. (biorxiv.org)
There is a relationship between protein aggregate structure (strain) and clinical phenotype in prion diseases, however, whether differences in the strains of α-synuclein aggregates account for the different pathologies remained unclear. (elifesciences.org)

We will use these pre-clinical models to investigate whether alpha-synuclein wildtype or PD-mutant A53T will be accumulated and deposited into Lewy body-like inclusions in the mutant dopamine neurons. (michaeljfox.org)

Mutations in alpha-synuclein are associated with early-onset familial Parkinson's disease and the protein aggregates abnormally in Parkinson's disease, Lewy body disease, and other neurodegenerative diseases. (wikipedia.org)

Further examination indicated that structural differences in the C-terminal region of α-synuclein strains lead to different effects on proteasome activity. (elifesciences.org)
These results provide a possible molecular mechanism to account for the different pathologies induced by different α-synuclein strains. (elifesciences.org)
Just as in the case of antibiotic resistance, new strains evolve within an infected immune-compromised person's body that produce a version of the spike protein that no longer binds with the acquired antibodies. (theepochtimes.com)

JUPITER, Fla.-In March, The Scripps Research Institute (TSRI) announced two significant neurological discoveries, one dealing with the genetics of depression and one involving a link between neuronal death and Lewy bodies in Parkinson's. (drugdiscoverynews.com)
Her research group has discovered a connection between neuronal death and Lewy bodies. (drugdiscoverynews.com)

These abnormal α-synuclein species exhibit seeding activity for prion-like conversion, being similar in this respect to the infectious forms of prion protein (PrP) causing Creutzfeldt-Jakob disease (CJD) and bovine spongiform encephalopathy ( Goedert, 2015 ). (elifesciences.org)

It's important to be aware that when Lewy bodies are broken down, these toxic substances may be created," Lasmézas said. (drugdiscoverynews.com)

Recombinant full-length tag-free human Alpha-synuclein (A53T) mutant Protein was expressed in E. coli cells. (signalchem.com)
SDS-PAGE of ~14 kDa Alpha Synuclein (A53T) Protein (Cat# S22-36N). (signalchem.com)

Lewy bodies were described a century ago, but it wasn't until 1997 that scientists discovered they were made of clumps of a misfolded protein called α-synuclein. (drugdiscoverynews.com)

Lewy bodies are intracytoplasmic eosinophilic inclusions, often with halos, that are easily seen in pigmented neurons, as shown in this histologic slide. (medscape.com)

We showed that PQQ dramatically inhibits the fibril formation of C-terminal truncated alpha-synuclein110119, and 133 as well as the mixtures of full-length alpha-synuclein with these truncated variants. (biomedcentral.com)

Alpha-synuclein119 aggregated more rapidly and enhanced significantly the fibril formation of alpha-synuclein. (biomedcentral.com)

The presence of inclusion bodies known as Papp-Lantos bodies, in the movement, balance, and autonomic-control centres of the brain are the defining histopathologic hallmark of MSA. (wikipedia.org)
Any problem with the functioning of the autonomic nervous system, which controls unconscious body functions that affect the bladder, bowels, sweating, sexual function and blood pressure. (michaeljfox.org)
The autonomic nervous system innervates and influences every organ in the body. (bmj.com)
This complex system is mediated by two major efferent pathways, the sympathetic and parasympathetic nervous systems, which obtain afferent signals from different parts of the body, neurons in the spinal cord and cerebral autonomic centres primarily in the hypothalamus, midbrain and brainstem. (bmj.com)

In severe cases," he wrote, "there may develop a peculiar tilting of the head, a marked dragging of one or both legs, a staggering, propulsive gait with the facial characteristics of the parkinsonian syndrome, or a backward swaying of the body, tremors, vertigo, and deafness. (jmc.qa)

Anatomy11

Organisms1

Diseases14

Chemicals and Drugs29

Analytical, Diagnostic and Therapeutic Techniques and Equipment3

Psychiatry and Psychology11

Phenomena and Processes7

Disciplines and Occupations1

Anthropology, Education, Sociology and Social Phenomena1

Information Science2

Dementia13

Fibrils11

Neurites6

Aggregation10

Inclusions known as Lewy bodies2

Proteins15

Cytoplasmic inclusions3

Accumulation8

Amyloid4

Intraneuronal aggregates1

Pathology1

Mutant alpha-synuclein1

Neurodegeneration3

Proteinaceous inclusions1

Pathological3

Dopaminergic4

Pathogenesis4

Alzheimer's1

Ubiquitin1

Natively unfolded protein2

Substantia nigra3

Hallmarks2

Spillantini1

SNCA4

Neurodegenerative disorders1

Cellular1

Mutation1

Overexpression1

20012

Exogenous1

Unclear2

Dopamine1

Abnormally1

Strains3

Neuronal death2

Abnormal1

Toxic1

A53T2

Clumps1

Intracytoplasmic1

Inhibits1

Fibril1

Autonomic4

Parkinsonian1