concept

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.

29Connections

20Hypotheses

3Analyses

18Outgoing

11Incoming

0Experiments

3Debates

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💡 Concept Info

Name	ALPHA_SYNUCLEIN
Key Genes/Proteins	BAG3, BMAL1, CNTNAP4, GBA, MHCII
Related Diseases	COGNITIVE_FUNCTION, NEURODEGENERATION
Related Pathways	ADAPTIVE_IMMUNITY, CA2_HOMEOSTASIS, INNATE_IMMUNITY

Pathway Diagram

graph TD
    ALPHA_SYNUCLEIN["ALPHA_SYNUCLEIN"]
    ALPHA_SYNUCLEIN -->|"causes"| PD["PD"]
    ALPHA_SYNUCLEIN -->|"causes"| DLBD["DLBD"]
    ALPHA_SYNUCLEIN -->|"causes"| MSA["MSA"]
    ALPHA_SYNUCLEIN -->|"contributes to"| lewy_bodies["lewy_bodies"]
    ALPHA_SYNUCLEIN -->|"causes"| DOPAMINERGIC_NEURONS["DOPAMINERGIC_NEURONS"]
    ALPHA_SYNUCLEIN -->|"regulates"| COGNITIVE_FUNCTION["COGNITIVE_FUNCTION"]
    ALPHA_SYNUCLEIN -->|"activates"| CD4_T_CELLS["CD4_T_CELLS"]
    ALPHA_SYNUCLEIN -->|"activates"| ASTROCYTES["ASTROCYTES"]
    SNCA["SNCA"] -->|"encodes"| ALPHA_SYNUCLEIN
    ASO["ASO"] -->|"inhibits"| ALPHA_SYNUCLEIN
    BAG3["BAG3"] -->|"inhibits"| ALPHA_SYNUCLEIN
    PLK2_PROTEIN["PLK2_PROTEIN"] -->|"regulates"| ALPHA_SYNUCLEIN
    BMAL1["BMAL1"] -->|"activates"| ALPHA_SYNUCLEIN
    CNTNAP4["CNTNAP4"] -->|"regulates"| ALPHA_SYNUCLEIN
    CEFTRIAXONE["CEFTRIAXONE"] -->|"inhibits"| ALPHA_SYNUCLEIN

Outgoing (18)

Target	Relation	Type	Str
Aggregation	causes	phenotype	0.90
PARKINSONS_DISEASE	associated_with	disease	0.87
PD	causes	disease	0.72
PARKINSON_DISEASE	associated_with	disease	0.72
DLBD	causes	disease	0.72
MSA	causes	disease	0.72
lewy_bodies	contributes_to	phenotype	0.72
calcium	regulates	protein	0.64
CD4_T_CELLS	activates	cell_type	0.64
CA2_HOMEOSTASIS	inhibits	pathway	0.64
DOPAMINERGIC_NEURONS	causes	cell_type	0.64
COGNITIVE_FUNCTION	regulates	phenotype	0.64
ASTROCYTES	activates	cell_type	0.64
NEURODEGENERATION	causes	phenotype	0.64
INNATE_IMMUNITY	activates	pathway	0.56
MHCII	activates	protein	0.56
ADAPTIVE_IMMUNITY	activates	pathway	0.56
protein_aggregation_pathway	participates_in	pathway	0.50

Incoming (11)

Source	Relation	Type	Str
SNCA	encodes	gene	1.00
SNCA	encodes	gene	1.00
ASO	inhibits	drug	0.87
GBA	interacts_with	gene	0.80
BAG3	inhibits	protein	0.72
PLK2_PROTEIN	regulates	protein	0.72
TGM2	causes	gene	0.70
BMAL1	activates	protein	0.64
CNTNAP4	regulates	gene	0.64
CEFTRIAXONE	inhibits	drug	0.64
GBA	suppresses	gene	0.60

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 (3)

Scientific analyses that reference this entity

What are the mechanisms by which gut microbiome dysbiosis influences Parkinson's

neurodegeneration | 2026-04-01 | 0 hypotheses

What are the mechanisms by which gut microbiome dysbiosis influences Parkinson's

neurodegeneration | 2026-04-01 | 13 hypotheses Top: 0.907

Protein aggregation cross-seeding across neurodegenerative diseases

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

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 (3)

Multi-agent debates referencing this entity

What are the mechanisms by which gut microbiome dysbiosis influences Parkinson's

closed · Rounds: 4 · Score: 0.95 · 2026-04-06

What are the mechanisms underlying what are the mechanisms by which gut microbio

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

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

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

Score: 0.626 · neurodegeneration · 2026-04-28

m6A-dependent control of alpha-synuclein transcript fate and aggregation kinetics should produce a measurable proximal p

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

Score: 0.620 · neurodegeneration · 2026-04-15

## Mechanistic Overview H7: Enteric Nervous System Alpha-Synuclein Propagation Blocker via Gut Barrier Restoration start

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

Score: 0.612 · neurodegeneration · 2026-04-28

The question is likely underpowered or misleading unless analyses preserve the key strata: m6A, RNA, N6-, alpha-synuclei

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

Score: 0.608 · neurodegeneration · 2026-04-28

The debate supports treating this as a validation program before ranking it as a therapy. Perturbation should move a pro

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

Score: 0.606 · neurodegeneration · 2026-04-25

Specific lipoprotein particles bind fibril surfaces and preserve polymorph architecture and seeding fidelity outside the

Ganglioside-rich extracellular vesicles preserve alpha-synuclein fibril conforma

Score: 0.582 · neurodegeneration · 2026-04-25

Membrane-derived cofactors in extracellular vesicles maintain polymorph fidelity and templating competence.

Neuronal Subtype-Specific Alpha-Synuclein Expression Normalization

Score: 0.571 · neurodegeneration · 2026-04-04

## Mechanistic Overview Neuronal Subtype-Specific Alpha-Synuclein Expression Normalization starts from the claim that mo

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

Score: 0.560 · neurodegeneration · 2026-04-24

The classic butyrate neuroprotection narrative likely depends on pharmacologic exposure sufficient for HDAC inhibition,

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

Score: 0.550 · neurodegeneration · 2026-04-24

A key liability hypothesis is that low-range SCFA signaling can be receptor-biased toward inflammasome activation in sus

Glucosylceramide accumulation nucleates alpha-synuclein aggregation via lipid ra

Score: 0.525 · Parkinson's disease · 2026-04-26

We propose that GBA deficiency-driven accumulation of glucosylceramide (GlcCer) in lysosomal membranes creates ordered l

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

Score: 0.489 · neurodegeneration · 2026-04-25

Electrostatic bridging by glycans and low-abundance proteins preserves disease-relevant fibril architecture.

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

Score: 0.440 · neurodegeneration · 2026-04-24

Propionate is the most plausible exploratory monotherapy candidate only because it may have somewhat more realistic syst

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

Score: 0.380 · proteomics · 2026-04-27

Parkinson's disease is characterized by the accumulation of misfolded alpha-synuclein protein aggregates (Lewy bodies) i