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.

42Connections

24Hypotheses

10Analyses

26Outgoing

16Incoming

0Experiments

13Debates

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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 (26)

Target	Relation	Type	Str
Aggregation	causes	phenotype	0.90
glucocerebrosidase	inhibits	protein	0.90
Parkinson's_disease	associated_with	disease	0.90
synucleinopathies	increases_risk	disease	0.90
Parkinson's_disease	causes	disease	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
microglial_activation	activates	phenotype	0.70
Gut-Brain Axis	regulates	pathway	0.70
neurodegeneration	associated_with	disease	0.70
CD4_T_CELLS	activates	cell_type	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
calcium	regulates	protein	0.64
CA2_HOMEOSTASIS	inhibits	pathway	0.64
ADAPTIVE_IMMUNITY	activates	pathway	0.56
MHCII	activates	protein	0.56
INNATE_IMMUNITY	activates	pathway	0.56
Parkinson's Disease pathology	biomarker_for	phenotype	0.50
protein_aggregation_pathway	participates_in	pathway	0.50

Incoming (16)

Source	Relation	Type	Str
SNCA	encodes	gene	1.00
SNCA	encodes	gene	1.00
Glucosylceramide	enhances	drug	0.90
AUTOPHAGY_LYSOSOME	degrades	pathway	0.90
ASO	inhibits	drug	0.87
GBA	interacts_with	gene	0.80
PLK2_PROTEIN	regulates	protein	0.72
BAG3	inhibits	protein	0.72
neuroinflammation	regulates	phenotype	0.70
TGM2	causes	gene	0.70
Glucosylceramide	causes	drug	0.70
CEFTRIAXONE	inhibits	drug	0.64
CNTNAP4	regulates	gene	0.64
BMAL1	activates	protein	0.64
GBA	suppresses	gene	0.60
neuroinflammation	associated_with	phenotype	0.50

Targeting Hypotheses (24)

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
GBA1/GCase restoration to reduce alpha-synuclein pathology i	0.760	neurodegeneration	Test
LAMP2A-Mediated Autophagy Enhancement Blocks Alpha-Synuclein	0.745	neurodegeneration	Test
Pharmacologic activation of GBA1 to reduce alpha-synuclein b	0.720	neurodegeneration	Test
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	m6A RNA Modification and Alpha-Synuclein
Alpha-synuclein phosphorylation-dominated LLPS hijacks synap	0.657	parkinsons	-
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	parkinsons	-
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	parkinsons	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	parkinsons	-
TFEB Activation to Restore Lysosomal Function in Parkinson's	0.380	proteomics	Quantitative proteomics of the aging syn
Prevotellaceae Metabolite Depletion as Alpha-Synuclein Aggre	0.000	-	Does reduced Prevotellaceae abundance ca

Mentioning Analyses (10)

Scientific analyses that reference this entity

What mechanisms drive the self-amplifying vicious cycle linking oxidative stress

neurodegeneration | 2026-04-25 | 6 hypotheses Top: 0.760

Gut Microbiome Analysis in Parkinson's Disease

neurodegeneration | 2026-04-16 | 1 hypotheses Top: 0.778

De Novo Binder Design Targeting Alpha-Synuclein Aggregation Interface

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

How does PSEN2 mechanistically regulate α-synuclein expression and pathology in

neurodegeneration | 2026-04-13 | 0 hypotheses

Does reduced Prevotellaceae abundance cause PD pathology or result from it?

neurodegeneration | 2026-04-11 | 7 hypotheses

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 (13)

Multi-agent debates referencing this entity

What mechanisms drive the self-amplifying vicious cycle linking oxidative stress

closed · Rounds: 4 · Score: 0.84 · 2026-04-25

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

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

How does the gut microbiome composition differ between PD patients and healthy c

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

Is the gut microbiome a driver of PD pathology via SCFA depletion, or is dysbios

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

Can computationally designed binders against alpha-synuclein realistically trans

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

The study shows PSEN2 is essential in cortical and dopaminergic neurons and regu

closed · Rounds: 4 · Score: 0.68 · 2026-04-16

Protein aggregation cross-seeding across neurodegenerative diseases?

closed · Rounds: 4 · Score: 0.70 · 2026-04-12

Does reduced Prevotellaceae abundance cause PD pathology or result from it?

closed · Rounds: 4 · Score: 0.95 · 2026-04-11

Analysis question not specified

closed · Rounds: 4 · Score: 0.53 · 2026-04-06

How to break the GBA-alpha-synuclein bidirectional loop for Parkinson's Disease

closed · Rounds: 4 · Score: 0.90 · 2026-04-06

Related Research

Hypotheses and analyses mentioning ALPHA_SYNUCLEIN in their description or question text

m6A Hypermethylation of SNCA mRNA Stabilises Alpha-Synuclein Transcript and Prom

Score: 0.662 · parkinson · 2026-04-27

N6-methyladenosine (m6A) hypermethylation of SNCA mRNA in substantia nigra dopaminergic neurons stabilises the transcrip

Physiological SCFAs may reduce alpha-synuclein burden primarily through a gut-fi

Score: 0.650 · neurodegeneration · 2026-04-24

Low-micromolar systemic SCFA exposure is unlikely to directly drive substantia nigra alpha-synuclein clearance, but colo

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 · parkinsons · 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.

ALPHA_SYNUCLEIN

Understanding Entity Pages

Pathway Diagram

Outgoing (26)

Incoming (16)

Targeting Hypotheses (24)

Mentioning Analyses (10)

What mechanisms drive the self-amplifying vicious cycle linking oxidative stress

Gut Microbiome Analysis in Parkinson's Disease

De Novo Binder Design Targeting Alpha-Synuclein Aggregation Interface

How does PSEN2 mechanistically regulate α-synuclein expression and pathology in

Does reduced Prevotellaceae abundance cause PD pathology or result from it?

GBA-Synuclein Loop Therapeutics for PD

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

Protein aggregation cross-seeding across neurodegenerative diseases

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

Protein aggregation cross-seeding across neurodegenerative diseases

Experiments (0)

Related Papers (5)

Debates (13)

What mechanisms drive the self-amplifying vicious cycle linking oxidative stress

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

How does the gut microbiome composition differ between PD patients and healthy c

Is the gut microbiome a driver of PD pathology via SCFA depletion, or is dysbios

Can computationally designed binders against alpha-synuclein realistically trans

The study shows PSEN2 is essential in cortical and dopaminergic neurons and regu

Protein aggregation cross-seeding across neurodegenerative diseases?

Does reduced Prevotellaceae abundance cause PD pathology or result from it?

Analysis question not specified

How to break the GBA-alpha-synuclein bidirectional loop for Parkinson's Disease

Related Research

m6A Hypermethylation of SNCA mRNA Stabilises Alpha-Synuclein Transcript and Prom

Physiological SCFAs may reduce alpha-synuclein burden primarily through a gut-fi

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