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.

1792Connections

20Hypotheses

10Analyses

50Outgoing

50Incoming

0Experiments

15Debates

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

→

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 (1018)

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

Incoming (774)

Source	Relation	Type	Str
entities-histone-deacetylase	interacts_with	wiki	0.00
entities-overview	interacts_with	wiki	0.00
entities-dna-methylation	interacts_with	wiki	0.00
entities-snx5	interacts_with	wiki	0.00
entities-gt-02287	interacts_with	wiki	0.00
ALPHA-SYNUCLEIN	encodes	gene	0.00
PARKINSON'S DISEASE	activates	gene	1.00
PARKINSON	associated_with	gene	1.00
SNCA	expresses	gene	1.00
NEURODEGENERATION	activates	gene	1.00
PARKINSON'S DISEASE	therapeutic_target	gene	1.00
PARKINSON'S DISEASE	associated_with	gene	1.00
PARKINSON	therapeutic_target	gene	1.00
SNCA	encodes	gene	0.95
PARKIN	regulates	gene	0.95
Autophagy	downregulates	process	0.95
LAG3	interacts_with	protein	0.95
SNCA	produces	gene	0.95
DNAJB6	inhibits	protein	0.90
16837598	has	paper	0.90
LAG3	binds	protein	0.90
SDA-2026-04-01-gap-20260401-225155	investigates	analysis	0.90
NLRP3 inflammasome	activates	pathway	0.90
LAG3	facilitates	protein	0.90
VINPOCETINE	attenuates	compound	0.90
PINK1	phosphorylates	gene	0.90
36085537	contributes to the degradation of	paper	0.90
40362234	is the cytopathological hallmark of	paper	0.90
TAU	interacts_with	protein	0.90
40362234	propagates from neuron to neuron in	paper	0.90
AFFITOPE PD01A	targets	drug	0.90
Cinpanemab	targets	drug	0.90
31358782	colocalizes with	paper	0.90
31358782	helps to facilitate	paper	0.90
31358782	modulates	paper	0.90
31358782	binds	paper	0.90
UB-312	targets	drug	0.90
Prasinezumab	targets	drug	0.90
PARKINSON	activates	gene	0.90
INFLAMMATION	activates	gene	0.90
NEURODEGENERATIVE DISEASES	associated_with	gene	0.90
NEURON	interacts_with	cell_type	0.86
NEURON	activates	cell_type	0.86
LRRK2	interacts_with	protein	0.85
Autophagy	mediates	process	0.85
APLP1	associated_with	protein	0.85
NNMT	causes_aggregation_of	gene	0.80
ANTISENSE OLIGONUCLEOTIDE (ASO)	reduces_expression	compound	0.80
BAG3	mediates	gene	0.80
HSPG2	promotes_aggregation_of	gene	0.80

Targeting Hypotheses (20)

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
m6A Hypermethylation of SNCA mRNA Stabilises Alpha-Synuclein	0.662	Parkinson disease	m6A RNA Modification and Alpha-Synuclein
Alpha-synuclein phosphorylation-dominated LLPS hijacks synap	0.657	Parkinson's disease	-
Physiological SCFAs may reduce alpha-synuclein burden primar	0.650	neurodegeneration	Do physiological concentrations of SCFAs

LRRK2 Haploinsufficiency Traps Microglia in Senescence-Like	0.650	Parkinson's disease	-
m6A-dependent control of alpha-synuclein transcript fate and	0.626	neurodegeneration	m6A RNA Modification and Alpha-Synuclein
H7: Enteric Nervous System Alpha-Synuclein Propagation Block	0.620	neurodegeneration	How does engineered C. butyricum cross t
Cell-state stratification is required to resolve m6A RNA Mod	0.612	neurodegeneration	m6A RNA Modification and Alpha-Synuclein
Perturbation-first validation should precede therapeutic cla	0.608	neurodegeneration	m6A RNA Modification and Alpha-Synuclein
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
Glucosylceramide accumulation nucleates alpha-synuclein aggr	0.525	Parkinson's disease	GBA-Synuclein Loop Therapeutics for PD
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
H2S/butyrate imbalance drives enteric alpha-synuclein pathol	0.380	Parkinson's disease	-
TFEB Activation to Restore Lysosomal Function in Parkinson's	0.380	proteomics	Quantitative proteomics of the aging syn

Mentioning Analyses (10)

Scientific analyses that reference this entity

Gut-Brain Axis in Parkinson's Disease: Molecular Mechanisms, Neuroinflammation,

neurodegeneration | 2026-04-26 | 4 hypotheses Top: 0.630

Analyze the spectrum of microglial activation states (DAM, homeostatic, inflamma

neurodegeneration | 2026-04-16 | 1 hypotheses Top: 0.627

Does RGS6 upregulation or D2 autoreceptor modulation prevent neurodegeneration i

neurodegeneration | 2026-04-16 | 0 hypotheses

De Novo Binder Design Targeting Alpha-Synuclein Aggregation Interface

neurodegeneration | 2026-04-16 | 1 hypotheses Top: 0.571

How does engineered C. butyricum cross the blood-brain barrier to directly bind

neurodegeneration | 2026-04-15 | 2 hypotheses Top: 0.699

Experiments (0)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
No experiments found

Related Papers (5)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year
Inhibition of autophagy in microglia and macrophages exacerbates innate immune r [PMID:36652438]	Hegdekar N, Sarkar C, Bustos S, Ritzel R	Autophagy	2023
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
Microglial NLRP3 inflammasome activates neurotoxic astrocytes in depression-like [PMID:36288697]	Li S, Fang Y, Zhang Y, Song M, Zhang X,	Cell reports	2022
Biomarker of Neuroinflammation in Parkinson's Disease. [PMID:35456966]	Liu TW, Chen CM, Chang KH	Int J Mol Sci	2022
NLRP3 inflammasome activation drives tau pathology. [PMID:31748742]	["Ising C", "Venegas C", "Zhang S", "Sch	Nature	2019

Debates (15)

Multi-agent debates referencing this entity

Hypothesis debate: SCFA Deficiency Disrupts Microglial Homeostasis and Promotes

closed · Rounds: 4 · Score: 0.60 · 2026-04-26

Hypothesis debate: Vagus Nerve as Anatomical Highway for Prion-Like α-Syn Propag

closed · Rounds: 4 · Score: 0.50 · 2026-04-26

Hypothesis debate: Enteric Nervous System Dysfunction as Self-Reinforcing Pathol

closed · Rounds: 4 · Score: 0.50 · 2026-04-26

Hypothesis debate: LPS-TLR4-NF-κB Signaling Cascade as Therapeutic Target

closed · Rounds: 4 · Score: 0.50 · 2026-04-26

What are the key molecular mechanisms by which gut microbiome dysbiosis drives n

closed · Rounds: 4 · Score: 1.00 · 2026-04-26

Can computational de novo protein binder design produce stable binders that bloc

closed · Rounds: 4 · Score: 0.70 · 2026-04-21

The core causation versus correlation debate remains unresolved despite being ce

closed · Rounds: 4 · Score: 0.50 · 2026-04-20

Analyze the spectrum of microglial activation states (DAM, homeostatic, inflamma

closed · Rounds: 4 · Score: 0.50 · 2026-04-20

While RGS6 deficiency causes Parkinson's-like pathology, whether enhancing RGS6

closed · Rounds: 4 · Score: 0.50 · 2026-04-18

Can computationally designed binders against alpha-synuclein realistically trans

closed · Rounds: 4 · Score: 0.70 · 2026-04-16

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 (1018)

Incoming (774)

Targeting Hypotheses (20)

Mentioning Analyses (10)

Gut-Brain Axis in Parkinson's Disease: Molecular Mechanisms, Neuroinflammation,

Analyze the spectrum of microglial activation states (DAM, homeostatic, inflamma

Does RGS6 upregulation or D2 autoreceptor modulation prevent neurodegeneration i

De Novo Binder Design Targeting Alpha-Synuclein Aggregation Interface

How does engineered C. butyricum cross the blood-brain barrier to directly bind

Why does iron chelation therapy worsen outcomes in H63D HFE variant carriers des

Does TFEB dysfunction causally drive neurodegeneration or represent compensatory

GBA-Synuclein Loop Therapeutics for PD

Autophagy-lysosome pathway convergence across neurodegenerative diseases

Protein aggregation cross-seeding across neurodegenerative diseases

Experiments (0)

Related Papers (5)

Debates (15)

Hypothesis debate: SCFA Deficiency Disrupts Microglial Homeostasis and Promotes

Hypothesis debate: Vagus Nerve as Anatomical Highway for Prion-Like α-Syn Propag

Hypothesis debate: Enteric Nervous System Dysfunction as Self-Reinforcing Pathol

Hypothesis debate: LPS-TLR4-NF-κB Signaling Cascade as Therapeutic Target

What are the key molecular mechanisms by which gut microbiome dysbiosis drives n

Can computational de novo protein binder design produce stable binders that bloc

The core causation versus correlation debate remains unresolved despite being ce

Analyze the spectrum of microglial activation states (DAM, homeostatic, inflamma

While RGS6 deficiency causes Parkinson's-like pathology, whether enhancing RGS6

Can computationally designed binders against alpha-synuclein realistically trans

Related Research

m6A-dependent control of alpha-synuclein transcript fate and aggregation kinetic

H7: Enteric Nervous System Alpha-Synuclein Propagation Blocker via Gut Barrier R

Cell-state stratification is required to resolve m6A RNA Modification and Alpha-

Perturbation-first validation should precede therapeutic claims for m6A RNA Modi

CSF ApoE- and clusterin-rich lipoprotein particles stabilize disease-relevant al

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

Glucosylceramide accumulation nucleates alpha-synuclein aggregation via lipid ra

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

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

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