gene

ALPHA-SYNUCLEIN

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about ALPHA-SYNUCLEIN: its mechanistic relationships (Knowledge Graph edges), hypotheses targeting it, analyses mentioning it, and supporting scientific papers. The interactive graph below shows its immediate neighbors. All content is AI-synthesized from peer-reviewed literature.

1767Connections

14Hypotheses

1Analyses

50Outgoing

50Incoming

6Experiments

1Debates

Summary

ALPHA-SYNUCLEIN is a gene implicated in neurodegeneration research. Key relationships include: associated with, activates, therapeutic target. Associated with ALS, Aging, Als. Connected to 529 entities in the SciDEX knowledge graph.

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🧬 Gene Info

Gene Symbol	ALPHA
Full Name	SYNUCLEIN
Chromosome	4q21.31
Protein Family	Synuclein family
Subcellular Localization	Presynaptic terminals, nucleus
Molecular Weight	14 kDa (140 aa)
Pathways	amyloid plaques, mTORC1, oxidative stress
UniProt ID	P37840
GeneCards	ALPHA
Human Protein Atlas	ALPHA
α-Syn-140	Full-length (140 aa) - predominant species in most tissues
α-Syn-126	Exon 3 skipped (126 aa) - lacks central region, less aggregation-prone
α-Syn-98	Exons 3 and 5 skipped (98 aa) - shortened, primarily in brain
α-Syn-115	Alternative splice variant (115 aa) - rare isoform
Associated Diseases	Aging, Als, Alzheimer, Alzheimer's Disease, Ataxia
Known Drugs/Compounds	DEXAMETHASONE, FINGOLIMOD, LITHIUM, proCTSD, RAPAMYCIN
Interactions	ACETYL-COA, ACLY, AGING, AKT, ALZHEIMER, ALZHEIMER DISEASE
KG Connections	1114 knowledge graph edges
Databases	GeneCards NCBI Gene HPA STRING

🔮 Predicted Structure: ALPHA-SYNUCLEIN — AlphaFold P37840 Click to expand

AI-predicted structure from AlphaFold | Powered by Mol*

Wiki Pages (1)

Knowledge base pages for this entity

Canonical Page

Alpha-Synuclein (α-Syn)

protein · 2462 words

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Pathway Diagram

graph TD
    ALPHA_SYNUCLEIN["ALPHA-SYNUCLEIN"] -->|"associated"| PARKINSON_S_DISEASE["PARKINSON'S DISEASE"]
    ALPHA_SYNUCLEIN["ALPHA-SYNUCLEIN"] -->|"activates"| INFLAMMATION["INFLAMMATION"]
    ALPHA_SYNUCLEIN["ALPHA-SYNUCLEIN"] -->|"associated"| ALS["ALS"]
    ALPHA_SYNUCLEIN["ALPHA-SYNUCLEIN"] -->|"associated"| SOD1["SOD1"]
    ALPHA_SYNUCLEIN["ALPHA-SYNUCLEIN"] -->|"associated"| DRD2["DRD2"]
    ALPHA_SYNUCLEIN["ALPHA-SYNUCLEIN"] -->|"associated"| AQP4["AQP4"]
    PARKIN["PARKIN"] -->|"regulates"| ALPHA_SYNUCLEIN["ALPHA-SYNUCLEIN"]
    PARKINSON_S_DISEASE_1["PARKINSON'S DISEASE"] -->|"regulates"| ALPHA_SYNUCLEIN["ALPHA-SYNUCLEIN"]
    MICROGLIA["MICROGLIA"] -->|"activates"| ALPHA_SYNUCLEIN["ALPHA-SYNUCLEIN"]
    PARKINSON_S_DISEASE_2["PARKINSON'S DISEASE"] -->|"associated"| ALPHA_SYNUCLEIN["ALPHA-SYNUCLEIN"]
    style ALPHA_SYNUCLEIN fill:#4a1a6b,stroke:#4fc3f7,stroke-width:2px,color:#e0e0e0

Outgoing (1001)

Target	Relation	Type	Str
ALPHA-SYNUCLEIN	encodes	protein	0.00
Parkinson	associated_with	disease	1.00
Parkinson	therapeutic_target	disease	1.00
Inflammation	activates	disease	1.00
Neurodegeneration	activates	disease	1.00
Parkinson	activates	disease	1.00
Neurodegeneration	therapeutic_target	disease	0.95
Lewy bodies	associated_with	phenotype	0.95
Lewy Body Formation	involved_in	process	0.95
DOPAMINERGIC NEURONS	contributes_to	cell_type	0.95
Mitochondrial Quality Control	modulates	pathway	0.95
Liquid-Liquid Phase Separation	involved_in	process	0.95
Parkinson's Disease	associated_with	disease	0.95
Synucleinopathies	causes	disease	0.95
PARKINSON'S DISEASE	associated_with	gene	0.95
Lewy Bodies	component_of	structure	0.95
Diffuse Lewy Body Disease	involved_in	disease	0.95
Multiple System Atrophy	involved_in	disease	0.95
Als	associated_with	disease	0.95
Als	activates	disease	0.95
Parkinson's Disease	associated_with	disease	0.95
Synucleinopathies	causes	disease	0.95
Lewy Bodies	associated_with	biomarker	0.95
NEURON	associated_with	cell_type	0.95
Dopaminergic Neurodegeneration	associated_with	process	0.93
NLRP3	activates	protein	0.93
MICROGLIA	activates	cell_type	0.92
Parkinson's Disease	causes	disease	0.90
Neurodegeneration	associated_with	process	0.90
toxic aggregation	causes	pathway	0.90
Dopaminergic Neuronal Loss	contributes_to	phenotype	0.90
Parkinson'S Disease	associated_with	disease	0.90
Parkinson	causes	disease	0.90
autophagy	inhibits	process	0.90
STAT1	activates	gene	0.90
PARKINSON'S DISEASE	associated_with	disease	0.90
Lewy Body Formation	causes	process	0.90
STING	activates	protein	0.90
Neurodegeneration	causes	process	0.90
NEUROINFLAMMATION	promotes	process	0.90
ACLY	activates	protein	0.90
Chaperone Proteins	correlates_with	protein	0.90
Neuroinflammation	causes	process	0.90
mTORC1	activates	pathway	0.90
substantia nigra	causes	brain_region	0.90
KV1.3	upregulates	gene	0.90
dopaminergic neurons	causes	cell_type	0.90
Autophagy	activates	pathway	0.90
NEURON	interacts_with	cell_type	0.86
NEURON	expressed_in	cell_type	0.85

Incoming (766)

Source	Relation	Type	Str
entities-overview	interacts_with	wiki	0.00
entities-snx5	interacts_with	wiki	0.00
entities-histone-deacetylase	interacts_with	wiki	0.00
entities-gt-02287	interacts_with	wiki	0.00
entities-dna-methylation	interacts_with	wiki	0.00
ALPHA-SYNUCLEIN	encodes	gene	0.00
PARKINSON'S DISEASE	therapeutic_target	gene	1.00
PARKINSON	associated_with	gene	1.00
PARKINSON'S DISEASE	activates	gene	1.00
NEURODEGENERATION	activates	gene	1.00
PARKINSON'S DISEASE	associated_with	gene	1.00
SNCA	expresses	gene	1.00
PARKINSON	therapeutic_target	gene	1.00
SNCA	produces	gene	0.95
LAG3	interacts_with	protein	0.95
Autophagy	downregulates	process	0.95
SNCA	encodes	gene	0.95
PARKIN	regulates	gene	0.95
PINK1	phosphorylates	gene	0.90
LAG3	facilitates	protein	0.90
VINPOCETINE	attenuates	compound	0.90
SDA-2026-04-01-gap-20260401-225155	investigates	analysis	0.90
40362234	propagates from neuron to neuron in	paper	0.90
40362234	is the cytopathological hallmark of	paper	0.90
LAG3	binds	protein	0.90
UB-312	targets	drug	0.90
Cinpanemab	targets	drug	0.90
AFFITOPE PD01A	targets	drug	0.90
36085537	contributes to the degradation of	paper	0.90
DNAJB6	inhibits	protein	0.90
Prasinezumab	targets	drug	0.90
TAU	interacts_with	protein	0.90
NEURODEGENERATIVE DISEASES	associated_with	gene	0.90
INFLAMMATION	activates	gene	0.90
PARKINSON	activates	gene	0.90
NEURON	interacts_with	cell_type	0.86
NEURON	activates	cell_type	0.86
APLP1	associated_with	protein	0.85
Autophagy	mediates	process	0.85
LRRK2	interacts_with	protein	0.85
VINPOCETINE	downregulates	compound	0.80
PINK1	associated_with	gene	0.80
MICROGLIA	associated_with	cell_type	0.80
HSPG2	promotes_aggregation_of	gene	0.80
BAG3	mediates_clearance	gene	0.80
proCTSD	targets	drug	0.80
BAG3	mediates	gene	0.80
GBA	regulates	gene	0.80
NNMT	causes_aggregation_of	gene	0.80
ANTISENSE OLIGONUCLEOTIDE (ASO)	reduces_expression	compound	0.80

Targeting Hypotheses (14)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
Astrocyte-Intrinsic NLRP3 Inflammasome Activation by Alpha-S	0.822	neurodegeneration	What are the mechanisms by which gut mic
A downstream LRRK2-Rab10-JIP4 lysosomal stress loop promotes	0.680	neurodegeneration	Do pathogenic LRRK2 mutations amplify vo
Physiological SCFAs may reduce alpha-synuclein burden primar	0.650	neurodegeneration	Do physiological concentrations of SCFAs
H7: Enteric Nervous System Alpha-Synuclein Propagation Block	0.620	neurodegeneration	How does engineered C. butyricum cross t
CSF ApoE- and clusterin-rich lipoprotein particles stabilize	0.606	neurodegeneration	Which specific CSF molecular components

Ganglioside-rich extracellular vesicles preserve alpha-synuc	0.582	neurodegeneration	Which specific CSF molecular components
Neuronal Subtype-Specific Alpha-Synuclein Expression Normali	0.571	neurodegeneration	De Novo Binder Design Targeting Alpha-Sy
Direct neuronal HDAC inhibition is unlikely to mediate thera	0.560	neurodegeneration	Do physiological concentrations of SCFAs
Physiological SCFAs may worsen alpha-synuclein pathology thr	0.550	neurodegeneration	Do physiological concentrations of SCFAs
Sulfated glycans and metal-binding CSF proteins brace alpha-	0.489	neurodegeneration	Which specific CSF molecular components
Propionate may outperform acetate or butyrate at physiologic	0.440	neurodegeneration	Do physiological concentrations of SCFAs
Glucosylceramide accumulation nucleates alpha-synuclein aggr	0.000	Parkinson's disease	GBA-Synuclein Loop Therapeutics for PD
H2S/butyrate imbalance drives enteric alpha-synuclein pathol	0.000	Parkinson's disease	-
TFEB Activation to Restore Lysosomal Function in Parkinson's	0.000	proteomics	Quantitative proteomics of the aging syn

Mentioning Analyses (1)

Scientific analyses that reference this entity

Protein aggregation cross-seeding across neurodegenerative diseases

neurodegeneration | 2026-04-01 | 7 hypotheses Top: 0.639

Experiments (6)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Model	Status	Est. Cost
Long-term perampanel treatment in A53T BAC-SNCA mice with PFF injectio	validation	Lewy body disease	0.950	A53T BAC-SNCA transgenic mice	proposed	N/A
Longitudinal TLR2 reporter gene study in α-synuclein mice	validation	Parkinson's disease	0.900	Thy1.2-α-synuclein transgenic	proposed	N/A
PFF uptake in primary hippocampal neurons with inhibitors	exploratory	Lewy body disease	0.900	mouse primary hippocampal neur	proposed	N/A
Dexamethasone treatment study in α-synuclein mice	validation	Parkinson's disease	0.850	Thy1.2-α-synuclein transgenic	proposed	N/A
PFF clearance kinetics in Snca knockout mice	validation	Lewy body disease	0.800	Snca knockout mice	proposed	N/A
TLR expression in α-synuclein overexpressing mice	validation	Parkinson's disease	0.800	mice overexpressing human α-sy	proposed	N/A

Related Papers (17)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
Meta-analysis of mRNA dysregulation associated with Parkinson's disease and othe [PMID:41183391]	Lin Aung T, Aung YW, Shi X	Biomed Phys Eng Express	2026	1
A human striatal-midbrain assembloid model of alpha-synuclein propagation. [PMID:40919647]	Tran HD, Shin MK, Yeo XY, Jung S, Junaid	Brain	2026	0
Neuronal titration of Snca via enhancer disruption mitigates disease onset in a [PMID:41496593]	Boyd RJ, Kho AR, McClymont SA, Loftus SK	Brain	2026	0
Perampanel Blocks Transsynaptic α-Synuclein Propagation and Neurodegeneration in [PMID:41508763]	Ueda J, Uemura N, Chang J, Hirato T, Ish	Mov Disord	2026	0
Analysis of α-synuclein seed amplification assay in carriers of GBA1 and LRRK2 p [PMID:41574889]	Fraser KB, Mirelman A, Mabrouk OS, Omer	J Parkinsons Dis	2026	0
Aberrant Protein S-Nitrosylation Mimics the Effect of Rare Genetic Mutations in [PMID:41635116]	Wang Y, Lipton SA	J Neurochem	2026	0
SNCA triplication disrupts proteostasis and extracellular architecture prior to [PMID:41698927]	Statoulla E, Zafeiri M, Chalkiadaki K, V	NPJ Parkinsons Dis	2026	0
Gene therapy targeting synaptopathy linked with Alzheimer's and Parkinson's dise [PMID:41730496]	Panda SP, Saraswat N, Singh V	Neuroscience	2026	0
Degradation of alpha-synuclein/SNCA mRNA by RNautophagy. [PMID:41747943]	Kabuta C, Hakuno F, Kataoka N, Takahashi	Neurochem Int	2026	0
An update on the monogenic causes of Parkinson's disease: Impact on patient stra [PMID:41759745]	Asmi S, Krishnan A, Alexander SM, Mohame	Ageing Res Rev	2026	0
N-acetyl-l-leucine lowers α-synuclein levels and improves synaptic function in P [PMID:41766663]	Song P, Chen C, Franchini R, Duong B, Wa	J Clin Invest	2026	0
Genome editing in Parkinson's disease: Unlocking therapeutic avenues through CRI [PMID:41905621]	["Singh R", "Maity P", "Jaiswal C"]	Neurochemistry international	2026	0
Inhibition of autophagy in microglia and macrophages exacerbates innate immune r [PMID:36652438]	Hegdekar N, Sarkar C, Bustos S, Ritzel R	Autophagy	2023	0
Parkin regulates microglial NLRP3 and represses neurodegeneration in Parkinson's [PMID:37029500]	Yan YQ, Zheng R, Liu Y, Ruan Y, Lin ZH,	Aging cell	2023	0
Microglial NLRP3 inflammasome activates neurotoxic astrocytes in depression-like [PMID:36288697]	Li S, Fang Y, Zhang Y, Song M, Zhang X,	Cell reports	2022	0
Biomarker of Neuroinflammation in Parkinson's Disease. [PMID:35456966]	Liu TW, Chen CM, Chang KH	Int J Mol Sci	2022	0
NLRP3 inflammasome activation drives tau pathology. [PMID:31748742]	["Ising C", "Venegas C", "Zhang S", "Sch	Nature	2019	0

Debates (1)

Multi-agent debates referencing this entity

What are the mechanisms underlying protein aggregation cross-seeding across neur

closed · Rounds: 4 · Score: 0.95 · 2026-04-01

Related Research

Hypotheses and analyses mentioning ALPHA-SYNUCLEIN in their description or question text

ALPHA-SYNUCLEIN

Understanding Entity Pages

Summary

Wiki Pages (1)

Alpha-Synuclein (α-Syn)

Pathway Diagram

Outgoing (1001)

Incoming (766)

Targeting Hypotheses (14)

Mentioning Analyses (1)

Protein aggregation cross-seeding across neurodegenerative diseases

Experiments (6)

Related Papers (17)

Debates (1)

What are the mechanisms underlying protein aggregation cross-seeding across neur

Related Research

Ganglioside-rich extracellular vesicles preserve alpha-synuclein fibril conforma

Neuronal Subtype-Specific Alpha-Synuclein Expression Normalization

Direct neuronal HDAC inhibition is unlikely to mediate therapeutic alpha-synucle

Physiological SCFAs may worsen alpha-synuclein pathology through FFAR2/GPR43-NLR

Sulfated glycans and metal-binding CSF proteins brace alpha-synuclein fibril pol

Propionate may outperform acetate or butyrate at physiological exposure, but mai

Glucosylceramide accumulation nucleates alpha-synuclein aggregation via lipid ra

TFEB Activation to Restore Lysosomal Function in Parkinson's Disease Alpha-Synuc