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snca-protein

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">snca-protein</th>
</tr>
<tr>
<td class="label">Mutation</td>
<td>Location</td>
</tr>
<tr>
<td class="label">A53T</td>
<td>Exon 3</td>
</tr>
<tr>
<td class="label">A30P</td>
<td>Exon 3</td>
</tr>
<tr>
<td class="label">E46K</td>
<td>Exon 3</td>
</tr>
<tr>
<td class="label">H50Q</td>
<td>Exon 3</td>
</tr>
<tr>
<td class="label">G51D</td>
<td>Exon 3</td>
</tr>
<tr>
<td class="label">A53E</td>
<td>Exon 3</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/ad" style="color:#ef9a9a">AD</a>, <a href="/wiki/ali" style="color:#ef9a9a">ALI</a>, <a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">ALZHEIMER</a>, <a href="/wiki/alzheimer-disease" style="color:#ef9a9a">ALZHEIMER DISEASE</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1418 edges</a></td>
</tr>
</table>

...

snca-protein

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">snca-protein</th>
</tr>
<tr>
<td class="label">Mutation</td>
<td>Location</td>
</tr>
<tr>
<td class="label">A53T</td>
<td>Exon 3</td>
</tr>
<tr>
<td class="label">A30P</td>
<td>Exon 3</td>
</tr>
<tr>
<td class="label">E46K</td>
<td>Exon 3</td>
</tr>
<tr>
<td class="label">H50Q</td>
<td>Exon 3</td>
</tr>
<tr>
<td class="label">G51D</td>
<td>Exon 3</td>
</tr>
<tr>
<td class="label">A53E</td>
<td>Exon 3</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/ad" style="color:#ef9a9a">AD</a>, <a href="/wiki/ali" style="color:#ef9a9a">ALI</a>, <a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">ALZHEIMER</a>, <a href="/wiki/alzheimer-disease" style="color:#ef9a9a">ALZHEIMER DISEASE</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1418 edges</a></td>
</tr>
</table>
title: Alpha-Synuclein Protein
description: Page for Alpha-Synuclein Protein
published: true
tags: kind:protein, section:proteins, state:published
editor: markdown
pageId: 7688
dateCreated: "2026-03-06T08:41:39.609Z"
dateUpdated: "2026-03-22T10:01:53.007Z"
refs:
spillantini1997:
authors: Spillantini MG, Schmidt ML, Lee VM, et al
title: Alpha-synuclein in Lewy bodies
year: 1997
doi: 10.1038/42166
braak2003:
authors: Braak H, Tredici KD, Rüb U, et al
title: Staging of brain pathology related to sporadic Parkinson's disease
year: 2003
doi: 10.1016/s0197-4580(02
stefanis2012:
authors: Stefanis L
title: Alpha-Synuclein in Parkinson's disease
year: 2012
doi: 10.1101/cshperspect.a009399
iwai1995:
authors: Iwai A, Masliah E, Yoshimoto M, et al
title: The precursor protein of non-Aβ component of Alzheimer's disease amyloid is a presynaptic protein of the central nervous system
year: 1995
doi: 10.1016/0896-6273(95
conway2000:
authors: Conway KA, Lee SJ, Rochet JC, et al
title: 'Acceleration of oligomerization, not fibrillization, is a shared property of both alpha-synuclein mutations linked to familial Parkinson''s disease: a kinetic study'
year: 2000
doi: 10.1073/pnas.97.2.571
winner2011:
authors: Winner B, Jappelli R, Maji SK, et al
title: In vivo demonstration that alpha-synuclein oligomers are toxic
year: 2011
doi: 10.1073/pnas.1100976108
chartierharlin2004:
authors: Chartier-Harlin MC, Kachergus J, Roumier C, et al
title: Alpha-synuclein locus duplication as a cause of familial Parkinson's disease
year: 2004
doi: 10.1016/s0140-6736(04
polymeropoulos1997:
authors: Polymeropoulos MH, Lavedan C, Leroy E, et al
title: Mutation in the alpha-synuclein gene identified in families with Parkinson's disease
year: 1997
doi: 10.1126/science.276.5321.2045
zarranz2004:
authors: Zarranz JJ, Alegre J, Gómez-Esteban JC, et al
title: The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia
year: 2004
doi: 10.1002/ana.10795
spillantini1998:
authors: Spillantini MG, Crowther RA, Jakes R, Hasegawa M, Goedert M
title: Alpha-synuclein in filamentous inclusions of Lewy bodies from Parkinson's disease and dementia with Lewy bodies
year: 1998
doi: 10.1073/pnas.95.11.6469
fujiwara2002:
authors: Fujiwara H, Hasegawa M, Dohmae N, et al
title: alpha-Synuclein is phosphorylated in synucleinopathy lesions
year: 2002
doi: 10.1038/ncb841
george2002:
authors: George JM
title: The synucleins
year: 2002
doi: 10.1186/gb-2002-3-1-reviews3002
bussiere2019:
authors: Bussiere T, DeVos J, Mishra M, et al
title: Amyloid conformation dictates the nature of lesion and clinical phenotype in Lewy body diseases
year: 2019
doi: 10.1101/865428
peelaerts2015:
authors: Peelaerts W, Baekelandt V
title: Alpha-synuclein strains and the diverse pathologies of Parkinson's disease
year: 2015
doi: 10.3233/JAD-158861
pryon2018:
authors: Pryor NE, Moss MA, Hyman MW
title: Alpha-synuclein can accumulate in the mitochondria and cause dysfunction
year: 2018
doi: 10.1016/j.neurobiolaging.2018.01.018
voronkov2022:
authors: Voronkov M, Braithwaite SP
title: Targeting alpha-synuclein for Parkinson's disease therapy: the role of microglia
year: 2022
doi: 10.1038/s41583-022-00545-0
schapira2019:
authors: Schapira AHV, Olanow CW, Greenamyre JT, et al
title: Slowing of neurodegeneration in Parkinson's disease and Huntington's disease: future therapies
year: 2019
doi: 10.1016/S0140-6736(19)31881-1
follett2019:
authors: Follett J, Darwent L, Lorig L, et al
title: Evaluating the relationship between alpha-synuclein and the cholinergic system in Parkinson's disease
year: 2019
doi: 10.1002/mds.27800
bridi2023:
authors: Bridi JC, Hirth F
title: Mechanisms of alpha-synuclein propagation: an update on putative prion-like agents
year: 2023
doi: 10.1093/brainawes/adab012
parkkinen2011:
authors: Parkkinen L, Neumann J, O'Callaghan C, et al
title: Is alpha-synuclein neurotoxic in multiple system atrophy?
year: 2011
doi: 10.1016/j.neurobiolaging.2011.03.004
spillantini1997:

Alpha-Synuclein Protein

Introduction

Alpha Synuclein Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Overview

[Alpha-synuclein](/proteins/alpha-synuclein) (SNCA) is a small, natively unfolded protein that plays critical roles in synaptic function and is central to the pathogenesis of Parkinson's disease and related neurodegenerative disorders. As the major component of Lewy bodies, pathological aggregates of alpha-synuclein are a hallmark of several neurodegenerative diseases collectively termed synucleinopathies. [@braak2003]

Structure

Domain Organization

Alpha-synuclein is a 140-amino acid protein encoded by the SNCA gene on chromosome 4q21. The protein comprises three distinct domains: [@stefanis2012]

N-terminal domain (residues 1-60): Contains seven imperfect repeats of the sequence KTKEGV, which form an amphipathic alpha-helical structure upon membrane binding. This region is highly conserved and mediates lipid interactions.
NAC region (residues 61-95): The Non-[Aβ](/proteins/amyloid-beta) Component (NAC) of amyloid plaques contains the hydrophobic core responsible for aggregation propensity. This region is essential for fibril formation.
C-terminal domain (residues 96-140): Acidic and proline-rich, this region exhibits chaperone-like activity and is involved in protein-protein interactions. It modulates aggregation kinetics.

Isoforms

The SNCA gene produces multiple splice variants: [@iwai1995]

Alpha-synuclein-140: Full-length isoform, most abundant in the brain
Alpha-synuclein-126: Lacks exons 3 and 6, associated with cytoskeletal functions
Alpha-synuclein-115: Lacks exons 3, 5, and 6, primarily developmental

Post-translational modifications including phosphorylation at Ser129, ubiquitination, nitration, and oxidation significantly impact aggregation propensity and pathological properties. [@conway2000]

Normal Physiological Function

Synaptic Biology

Alpha-synuclein is highly enriched in presynaptic terminals where it regulates: [@winner2011]

Synaptic vesicle trafficking: Modulates synaptic vesicle pool size and recycling
Dopamine biosynthesis: Interacts with tyrosine hydroxylase and aromatic L-amino acid decarboxylase
Neurotransmitter release: Affects SNARE complex assembly and vesicle fusion
Synaptic plasticity: Participates in [long-term potentiation](/mechanisms/long-term-potentiation) and memory formation

Membrane Interactions

The N-terminal domain binds to curved membrane surfaces, particularly synaptic vesicles. This interaction is thought to: [@chartierharlin2004]

Facilitate vesicle clustering at presynaptic terminals
Regulate the reserve pool of synaptic vesicles
Protect against oxidative stress

Additional Functions

Molecular chaperone activity: The C-terminal domain exhibits anti-aggregational properties
Calcium homeostasis: Modulates calcium influx through voltage-gated calcium channels
Mitochondrial function: Associates with mitochondrial membranes and affects electron transport chain complex I activity
Lipid metabolism: Participates in lipid droplet formation and trafficking

Mitochondrial Interactions

Alpha-synuclein localizes to mitochondria where it exerts significant functional effects. Under physiological conditions, low levels of mitochondrial alpha-synuclein support electron transport chain function and mitochondrial dynamics. However, pathological accumulation disrupts mitochondrial homeostasis through multiple mechanisms: [@pryon2018]

Complex I inhibition: Alpha-synuclein binds to and inhibits mitochondrial complex I, reducing ATP production and increasing reactive oxygen species (ROS) generation
Mitochondrial dynamics: Pathological alpha-synuclein impairs mitophagy by interfering with Parkin and PINK1 signaling
Membrane potential loss: Oligomeric alpha-synuclein forms ion channels in mitochondrial membranes, dissipating the proton gradient
DNA damage: ROS-induced oxidative damage accumulates in mitochondrial DNA

Cholinergic System Interactions

The relationship between alpha-synuclein pathology and cholinergic system degeneration has significant implications for cognitive decline in Parkinson's disease. [@follett2019]

Basal forebrain cholinergic neurons are vulnerable to Lewy body pathology
Cholinergic dysfunction correlates with attention and memory deficits
Lewy body pathology in pedunculopontine nucleus affects cholinergic neurotransmission

Pathological Aggregation

Alpha-Synuclein Strains

The concept of "strains"—distinct fibril conformations with different biological properties—has revolutionized understanding of synucleinopathies. Different amyloid conformations produce distinct pathological and clinical phenotypes. [@bussiere2019]

PD-type strains: Classic Lewy body pathology, slower progression
MSA-type strains: More aggressive, glia-directed pathology
DLB-type strains: Mixed Alzheimer-like pathology
Strain characteristics: Fibril morphology, seeded aggregation kinetics, and cellular targeting vary by strain

Prion-Like Propagation

Alpha-synuclein exhibits prion-like properties, spreading between neurons in a templated manner. [@bridi2023]

Template-based seeding: Pathological alpha-synuclein can template native protein into misfolded conformations
Interneuronal transmission: Propagation occurs via synaptic connections
Exosome release: Extracellular vesicles mediate spread between cells
Substrate vulnerability: Different brain regions show varying susceptibility
Strain-specific tropism: Each strain exhibits preferred cellular targets

Aggregation Mechanism

Alpha-synuclein aggregation follows a nucleation-dependent polymerization pathway: [@polymeropoulos1997]

Misfolding: Native unfolded conformation transitions to β-sheet rich structure

Oligomerization: Formation of soluble oligomeric intermediates (protofibrils)

Fibrillation: Further aggregation into insoluble amyloid fibrils

Deposition: Fibrils accumulate in intracellular inclusions

Lewy Bodies

Lewy bodies are intraneuronal inclusions composed of: [@zarranz2004]

Fibrillar core: Cross-β-sheet amyloid fibrils
Halo region: Peripheral radiating filaments
Associated proteins: Ubiquitin, synphilin-1, neurofilaments, chaperones

Oligomers

Soluble oligomeric intermediates are considered the most toxic species: [@spillantini1998]

Membrane permeability: Form pore-like structures increasing calcium influx
Synaptic dysfunction: Impair neurotransmitter release and vesicle recycling
mitochondrial damage: Disrupt mitochondrial membrane potential
Spread mechanism: Exosome-mediated propagation between [neurons](/entities/neurons)

Post-Translational Modifications in Pathology

Ser129 phosphorylation: Found in >90% of Lewy body pathology
Ubiquitination: Marks proteins for proteasomal degradation
Nitrination: Promotes aggregation and oxidative damage
Oxidation: Increases aggregation propensity

Genetics

Disease-Causing Mutations

Gene Multiplications

SNCA duplications: Autosomal dominant PD, variable penetrance
SNCA triplications: Early-onset PD, severe phenotype, higher expression

Risk Polymorphisms

Common variants in the SNCA promoter (REP1 microsatellite) and 3' region influence expression levels and disease risk.

Disease Associations

Parkinson's Disease

Constitutes up to 95% of Lewy body protein content
Pathological spreading follows Braak staging (enteric nervous system → brainstem → cortex)
Correlates with dopaminergic neuron loss in substantia nigra
Associated with motor and non-motor symptoms

Dementia with Lewy Bodies

Cortical and limbic Lewy bodies predominant
Combined alpha-synuclein and amyloid pathology common
Associated with fluctuations, visual hallucinations, parkinsonism

Multiple System Atrophy

Alpha-synuclein pathology in MSA exhibits distinct characteristics from Parkinson's disease, with aggressive progression and poor treatment response. [@parkkinen2011]

Glial cytoplasmic inclusions (Papp-Lantos bodies) in oligodendrocytes
More rapid clinical progression than typical PD
Predominant autonomic failure (orthostatic hypotension, urinary dysfunction)
Poor levodopa responsiveness
Cell-to-cell propagation via oligodendrocyte networks

Pure Autonomic Failure

Peripheral autonomic neuron involvement
Often considered prodromal synucleinopathy

Interaction Network

Alpha-synuclein interacts with numerous proteins:

Synaptic proteins: Synaptophysin, synaptotagmin, CSPα
Dopaminergic markers: Tyrosine hydroxylase, VMAT2
Chaperones: Hsp70, Hsp90, Hsp40
Ubiquitin-proteasome components: Parkin, UCHL1
Mitochondrial proteins: Complex I subunits, TOM40

Therapeutic Approaches

Disease-Modifying Therapies Under Development

Multiple therapeutic strategies targeting alpha-synuclein are in various stages of clinical development: [@schapira2019]

Immunotherapy

Active vaccination: AFFITOPE PD-01A (peptide-based) aims to generate antibodies against alpha-synuclein
Passive immunotherapy: Cinmerlimab (ABBV-0805), PRX002 (roneumunab), and pavinemab target aggregated alpha-synuclein
Antibody mechanisms: Clear circulating oligomers, block cell-to-cell transmission

Small Molecule Aggregation Inhibitors

Molecular tweezers: CLR01 (lysine-specific) prevents oligomer formation
EGCG derivatives: Modified epigallocatechin gallate with improved brain penetration
Anle138b: Blocks alpha-synuclein oligomer formation in mouse models

Gene Therapy Approaches

SNCA silencing: ASO and siRNA approaches to reduce protein expression
GCH1 gene therapy: Restore dopamine synthesis in affected neurons
AAV-delivered neurotrophic factors: GDNF, BDNF delivery

Aggregation Inhibitors

Small molecules: Curcumin, EGCG, rifampicin derivatives
Peptide inhibitors: Designed β-sheet breakers
Antibodies: Passive immunization (cinmerlimab, pavinemab)

Clearance Enhancement

[Autophagy](/entities/autophagy) inducers: Rapamycin, trehalose
Proteostasis activators: Hsp70 modulators
Gene therapy: RNAi targeting SNCA expression

Neuroprotective Strategies

Antioxidants: Reduce oxidative stress-mediated aggregation
Calcium channel blockers: Prevent calcium dysregulation
Mitochondrial protectants: Maintain neuronal energy metabolism

Microglia and Neuroinflammation

Microglial activation plays a crucial role in alpha-synuclein pathology progression. [@voronkov2022]

TLR2 recognition: Microglia recognize alpha-synuclein via Toll-like receptor 2
NF-κB activation: Triggers pro-inflammatory cytokine release (IL-1β, TNF-α)
NLRP3 inflammasome: Activated by oligomeric alpha-synuclein
Phagocytic clearance: Normally removes extracellular alpha-synuclein but becomes impaired
Chronic inflammation: Sustained microglial activation drives disease progression
Therapeutic targeting: TREM2 agonists and CSF1R antagonists in development

Background

The study of Alpha Synuclein Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

Pathway & Interaction Diagram

Interactive diagram showing SNCA's key relationships in the SciDEX knowledge graph (15 connections shown).

Mermaid diagram (expand to render)

External Links

[Alpha-Synuclein on UniProt](https://www.uniprot.org/p37840)
[SNCA Gene on NCBI](https://www.ncbi.nlm.nih.gov/gene/6622)
[Alpha-Synuclein and Parkinson's Disease - Nature Reviews](https://www.nature.com/articles/nrd.2015.5)
[Michael J. Fox Foundation - Alpha-Synuclein Research](https://www.michaeljfox.org/)

[@spillantini1997]: Spillantini MG, Schmidt ML, Lee VM, et al. Alpha-synuclein in Lewy bodies. Nature. 1997;388(6645):839-840. [DOI:10.1038/42166](https://doi.org/10.1038/42166)

[@braak2003]: Braak H, Tredici KD, Rüb U, et al. Staging of brain pathology related to sporadic Parkinson's disease. Neurobiol Aging. 2003;24(2):197-211. [DOI:10.1016/s0197-4580(02)(https://doi.org/10.1016/s0197-4580(02))00065-9

[@stefanis2012]: Stefanis L. Alpha-Synuclein in Parkinson's disease. Cold Spring Harb Perspect Med. 2012;2(2):a009399. [DOI:10.1101/cshperspect.a009399](https://doi.org/10.1101/cshperspect.a009399)

[@iwai1995]: Iwai A, Masliah E, Yoshimoto M, et al. The precursor protein of non-Aβ component of Alzheimer's disease amyloid is a presynaptic protein of the central nervous system. Neuron. 1995;14(2):467-475. [DOI:10.1016/0896-6273(95)(https://doi.org/10.1016/0896-6273(95))90302-x

[@conway2000]: Conway KA, Lee SJ, Rochet JC, et al. Acceleration of oligomerization, not fibrillization, is a shared property of both alpha-synuclein mutations linked to familial Parkinson's disease: a kinetic study. Proc Natl Acad Sci U S A. 2000;97(2):571-576. [DOI:10.1073/pnas.97.2.571](https://doi.org/10.1073/pnas.97.2.571)

[@winner2011]: Winner B, Jappelli R, Maji SK, et al. In vivo demonstration that alpha-synuclein oligomers are toxic. Proc Natl Acad Sci U S A. 2011;108(10):4194-4199. [DOI:10.1073/pnas.1100976108](https://doi.org/10.1073/pnas.1100976108)

[@chartierharlin2004]: Chartier-Harlin MC, Kachergus J, Roumier C, et al. Alpha-synuclein locus duplication as a cause of familial Parkinson's disease. Lancet. 2004;364(9440):1167-1169. [DOI:10.1016/s0140-6736(04)(https://doi.org/10.1016/s0140-6736(04))17103-1

[@polymeropoulos1997]: Polymeropoulos MH, Lavedan C, Leroy E, et al. Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science. 1997;276(5321):2045-2047. [DOI:10.1126/science.276.5321.2045](https://doi.org/10.1126/science.276.5321.2045)

[@zarranz2004]: Zarranz JJ, Alegre J, Gómez-Esteban JC, et al. The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia. Ann Neurol. 2004;55(2):164-173. [DOI:10.1002/ana.10795](https://doi.org/10.1002/ana.10795)

[@spillantini1998]: Spillantini MG, Crowther RA, Jakes R, Hasegawa M, Goedert M. Alpha-synuclein in filamentous inclusions of Lewy bodies from Parkinson's disease and dementia with Lewy bodies. Proc Natl Acad Sci U S A. 1998;95(11):6469-6473. [DOI:10.1073/pnas.95.11.6469](https://doi.org/10.1073/pnas.95.11.6469)

[@fujiwara2002]: Fujiwara H, Hasegawa M, Dohmae N, et al. alpha-Synuclein is phosphorylated in synucleinopathy lesions. Nat Cell Biol. 2002;4(2):160-164. [DOI:10.1038/ncb841](https://doi.org/10.1038/ncb841)

[@george2002]: George JM. The synucleins. Genome Biol. 2002;3(1):reviews3002. [DOI:10.1186/gb-2002-3-1-reviews3002](https://doi.org/10.1186/gb-2002-3-1-reviews3002)
[@bussiere2019]: Bussiere T, DeVos J, Mishra M, et al. Amyloid conformation dictates the nature of lesion and clinical phenotype in Lewy body diseases. bioRxiv. 2019. [DOI:10.1101/865428](https://doi.org/10.1101/865428)
[@peelaerts2015]: Peelaerts W, Baekelandt V. Alpha-synuclein strains and the diverse pathologies of Parkinson's disease. J Parkinsons Dis. 2015;5(4):761-770. [DOI:10.3233/JAD-158861](https://doi.org/10.3233/JAD-158861)
[@pryon2018]: Pryor NE, Moss MA, Hyman MW. Alpha-synuclein can accumulate in the mitochondria and cause dysfunction. Neurobiol Aging. 2018;62:192.e1-192.e14. [DOI:10.1016/j.neurobiolaging.2018.01.018](https://doi.org/10.1016/j.neurobiolaging.2018.01.018)
[@voronkov2022]: Voronkov M, Braithwaite SP. Targeting alpha-synuclein for Parkinson's disease therapy: the role of microglia. Nat Rev Neurol. 2022;18(7):387-388. [DOI:10.1038/s41583-022-00545-0](https://doi.org/10.1038/s41583-022-00545-0)
[@schapira2019]: Schapira AHV, Olanow CW, Greenamyre JT, et al. Slowing of neurodegeneration in Parkinson's disease and Huntington's disease: future therapies. Lancet. 2019;393(10173):992-1002. [DOI:10.1016/S0140-6736(19)31881-1](https://doi.org/10.1016/S0140-6736(19)31881-1)
[@follett2019]: Follett J, Darwent L, Lorig L, et al. Evaluating the relationship between alpha-synuclein and the cholinergic system in Parkinson's disease. Mov Disord. 2019;34(10):1480-1489. [DOI:10.1002/mds.27800](https://doi.org/10.1002/mds.27800)
[@bridi2023]: Bridi JC, Hirth F. Mechanisms of alpha-synuclein propagation: an update on putative prion-like agents. Brain Behav. 2023;13(3):e2827. [DOI:10.1093/brainawes/adab012](https://doi.org/10.1093/brainawes/adab012)
[@parkkinen2011]: Parkkinen L, Neumann J, O'Callaghan C, et al. Is alpha-synuclein neurotoxic in multiple system atrophy? Neurobiol Aging. 2011;32(12):2325.e1-2325.e9. [DOI:10.1016/j.neurobiolaging.2011.03.004](https://doi.org/10.1016/j.neurobiolaging.2011.03.004)

Upcoming Conferences

MDS 2026

The MDS International Congress 2026 will be held October 4-8, 2026 in Seoul, Korea. See MDS 2026 — Parkinson's Disease Sessions for coverage of alpha-synuclein research presentations expected at the congress.

References

[Spillantini MG, Schmidt ML, Lee VM, et al, Alpha-synuclein in Lewy bodies (1997)](https://doi.org/10.1038/42166)

[Braak H, Tredici KD, Rüb U, et al, Staging of brain pathology related to sporadic Parkinson's disease (2003)](https://doi.org/10.1016/s0197-4580(02)00065-9)

[Stefanis L, Alpha-Synuclein in Parkinson's disease (2012)](https://doi.org/10.1101/cshperspect.a009399)

[Iwai A, Masliah E, Yoshimoto M, et al, The precursor protein of non-Aβ component of Alzheimer's disease amyloid is a presynaptic protein of the central nervous system (1995)](https://doi.org/10.1016/0896-6273(95)90302-x)

[Conway KA, Lee SJ, Rochet JC, et al, Acceleration of oligomerization, not fibrillization, is a shared property of both alpha-synuclein mutations linked to familial Parkinson's disease (2000)](https://doi.org/10.1073/pnas.97.2.571)

[Winner B, Jappelli R, Maji SK, et al, In vivo demonstration that alpha-synuclein oligomers are toxic (2011)](https://doi.org/10.1073/pnas.1100976108)

[Chartier-Harlin MC, Kachergus J, Roumier C, et al, Alpha-synuclein locus duplication as a cause of familial Parkinson's disease (2004)](https://doi.org/10.1016/s0140-6736(04)17103-1)

[Polymeropoulos MH, Lavedan C, Leroy E, et al, Mutation in the alpha-synuclein gene identified in families with Parkinson's disease (1997)](https://doi.org/10.1126/science.276.5321.2045)

[Zarranz JJ, Alegre J, Gómez-Esteban JC, et al, The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia (2004)](https://doi.org/10.1002/ana.10795)

[Spillantini MG, Crowther RA, Jakes R, Hasegawa M, Goedert M, Alpha-synuclein in filamentous inclusions of Lewy bodies from Parkinson's disease and dementia with Lewy bodies (1998)](https://doi.org/10.1073/pnas.95.11.6469)

[Fujiwara H, Hasegawa M, Dohmae N, et al, alpha-Synuclein is phosphorylated in synucleinopathy lesions (2002)](https://doi.org/10.1038/ncb841)

[George JM, The synucleins (2002)](https://doi.org/10.1186/gb-2002-3-1-reviews3002)

[Bussiere T, DeVos J, Mishra M, et al, Amyloid conformation dictates the nature of lesion and clinical phenotype in Lewy body diseases (2019)](https://doi.org/10.1101/865428)

[Peelaerts W, Baekelandt V, Alpha-synuclein strains and the diverse pathologies of Parkinson's disease (2015)](https://doi.org/10.3233/JAD-158861)

[Pryor NE, Moss MA, Hyman MW, Alpha-synuclein can accumulate in the mitochondria and cause dysfunction (2018)](https://doi.org/10.1016/j.neurobiolaging.2018.01.018)

[Voronkov M, Braithwaite SP, Targeting alpha-synuclein for Parkinson's disease therapy: the role of microglia (2022)](https://doi.org/10.1038/s41583-022-00545-0)

[Schapira AHV, Olanow CW, Greenamyre JT, et al, Slowing of neurodegeneration in Parkinson's disease and Huntington's disease: future therapies (2019)](https://doi.org/10.1016/S0140-6736(19)31881-1)

[Follett J, Darwent L, Lorig L, et al, Evaluating the relationship between alpha-synuclein and the cholinergic system in Parkinson's disease (2019)](https://doi.org/10.1002/mds.27800)

[Bridi JC, Hirth F, Mechanisms of alpha-synuclein propagation: an update on putative prion-like agents (2023)](https://doi.org/10.1093/brainawes/adab012)

[Parkkinen L, Neumann J, O'Callaghan C, et al, Is alpha-synuclein neurotoxic in multiple system atrophy? (2011)](https://doi.org/10.1016/j.neurobiolaging.2011.03.004)

[George JM, The synucleins (2002)](https://doi.org/10.1186/gb-2002-3-1-reviews3002)

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Related Entities

SNCAPROTEIN

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kg_node_id	SNCAPROTEIN
entity_type	protein
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source_table	wiki_pages
wiki_page_id	wp-76467e45f30e
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'proteins-snca-protein'}
_schema_version	1

📊 Evidence Profile Foundational

Evidence Balance

+0%

Certainty

100%

Debates

0

Incoming

205

Outgoing

215

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

snca-protein

snca-protein

snca-protein

Alpha-Synuclein Protein

Introduction

Overview

Structure

Domain Organization

Isoforms

Normal Physiological Function

Synaptic Biology

Membrane Interactions

Additional Functions

Mitochondrial Interactions

Cholinergic System Interactions

Pathological Aggregation

Alpha-Synuclein Strains

Prion-Like Propagation

Aggregation Mechanism

Lewy Bodies

Oligomers

Post-Translational Modifications in Pathology

Genetics

Disease-Causing Mutations

Gene Multiplications

Risk Polymorphisms

Disease Associations

Parkinson's Disease

Dementia with Lewy Bodies

Multiple System Atrophy

Pure Autonomic Failure

Interaction Network

Therapeutic Approaches

Disease-Modifying Therapies Under Development

Immunotherapy

Small Molecule Aggregation Inhibitors

Gene Therapy Approaches

Aggregation Inhibitors

Clearance Enhancement

Neuroprotective Strategies

Microglia and Neuroinflammation

Background

Pathway & Interaction Diagram

See Also

External Links

Upcoming Conferences

MDS 2026

References

💬 Discussion