concept

Α-SYNUCLEIN

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about Α-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.

855Connections

15Hypotheses

2Analyses

50Outgoing

50Incoming

2Experiments

2Debates

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💡 Concept Info

Name	Α-SYNUCLEIN
Key Genes/Proteins	G2019S LRRK2, GBA1, HSC70
Related Diseases	Alzheimer's Disease, Dementia With Lewy Bodies, Dopaminergic Cell Dysfunction, Huntington's Disease

Wiki Pages (1)

Knowledge base pages for this entity

Canonical Page

ESCRT-III Inhibition by Alpha-Synuclein in Neurodegeneration

mechanism · 2580 words

→

Pathway Diagram

graph TD
    __SYNUCLEIN["Alpha-SYNUCLEIN"]
    style __SYNUCLEIN fill:#1a237e,stroke:#4fc3f7,stroke-width:3px
    __SYNUCLEIN -->|"causes"| Parkinson_s_Disease["Parkinson's Disease"]
    __SYNUCLEIN -->|"component_of"| Lewy_Pathology(Lewy Pathology)
    __SYNUCLEIN -.->|"biomarker for"| Dementia_With_Lewy_Bodies["Dementia With Lewy Bodies"]
    __SYNUCLEIN -->|"contributes to"| Neurodegeneration["Neurodegeneration"]
    __SYNUCLEIN -->|"involved_in"| Protein_Assembly["Protein Assembly"]
    __SYNUCLEIN -->|"causes"| Dopaminergic_Cell_Dysfunction(Dopaminergic Cell Dysfunction)
    __SYNUCLEIN -->|"upregulates"| Tunnelling_Nanotubes["Tunnelling Nanotubes"]
    __SYNUCLEIN -->|"causes"| Neuroinflammation["Neuroinflammation"]
    __SYNUCLEIN -->|"expressed in"| Cerebrospinal_Fluid["/Cerebrospinal Fluid/"]
    SNCA([SNCA]) -->|"encodes"| __SYNUCLEIN
    Tunnelling_Nanotubes -->|"mediates"| __SYNUCLEIN
    SQSTM1["SQSTM1"] -->|"mediates"| __SYNUCLEIN
    SNCA_ASOs{"SNCA ASOs"} -.->|"inhibits"| __SYNUCLEIN
    Antisense_Oligonucleotides{"Antisense Oligonucleotides"} -.->|"downregulates"| __SYNUCLEIN
    UBIQUITIN["UBIQUITIN"] -->|"interacts"| __SYNUCLEIN
    LC3["LC3"] -->|"mediates"| __SYNUCLEIN
    TAU([TAU]) -->|"stabilizes"| __SYNUCLEIN
    ALZHEIMER([ALZHEIMER]) -->|"stabilizes"| __SYNUCLEIN
    AGING([AGING]) -->|"stabilizes"| __SYNUCLEIN

Outgoing (252)

Target	Relation	Type	Str
h-90b7b77f59	targeted_by	hypothesis	1.00
Parkinson's disease	contributes_to	disease	0.95
Lewy bodies	component_of	structure	0.95
Lewy Pathology	component_of	phenotype	0.95
Neurodegeneration	contributes_to	process	0.95
Parkinson's Disease	biomarker_for	disease	0.95
Parkinson's Disease	contributes_to	disease	0.95
Parkinson's Disease	causes	disease	0.95
Microglia	activates	cell_type	0.95
Parkinson's Disease	causes	disease	0.95
Parkinson'S Disease	associated_with	disease	0.95
Dementia With Lewy Bodies	biomarker_for	disease	0.95
Parkinson's Disease	biomarker_for	disease	0.95
Parkinson's Disease	biomarker_for	disease	0.95
Neuronal-Microglial Tunnelling Nanotubes	upregulates	process	0.90
Dopaminergic Cell Dysfunction	causes	phenotype	0.90
Parkinson's Disease	associated_with	disease	0.90
Macroautophagy	substrate_of	process	0.90
Mitochondrial Dysfunction	causes	process	0.90
Microglia	interacts_with	cell_type	0.90
dopaminergic neuron degeneration	causes	process	0.90
Neuroinflammation	contributes_to	process	0.90
Neurodegeneration	contributes_to	process	0.90
Protein Assembly	involved_in	process	0.90
RNA G-quadruplex	binds	compound	0.90
Lewy Bodies	involved_in	phenotype	0.90
DOPAMINERGIC NEURONAL DYSFUNCTION	causes	process	0.90
PARKINSON'S DISEASE	biomarker_for	disease	0.90
Kii Als/Pdc	biomarker_for	disease	0.85
NLRP3 INFLAMMASOME	activates	pathway	0.85
Phosphorylation	involved_in	process	0.85
Sumoylation	involved_in	process	0.85
Nitration	involved_in	process	0.85
Neurogenesis	inhibits	process	0.85
Microglia	expressed_in	cell_type	0.85
Ubiquitination	involved_in	process	0.85
Neuroinflammation	causes	process	0.85
Central Nervous System Inflammation	causes	process	0.85
Cerebrospinal Fluid	expressed_in	cell_type	0.85
Dopaminergic Neurons	causes	cell_type	0.85
Macrophages	expressed_in	cell_type	0.85
NLRP3 Inflammasome Activation	activates	mechanism	0.85
M1-like Phenotype Polarization	causes	phenotype	0.85
Parkinson's Disease	associated_with	disease	0.85
Mitophagy	inhibits	process	0.85
pathological seeds	associated_with	protein	0.85
Synaptic Dysfunction	causes	phenotype	0.85
Mitochondria	causes	cell_type	0.85
Mitochondrial Fusion-Fission	modulates	process	0.80
Mitochondrial Transport	modulates	process	0.80

Incoming (603)

Source	Relation	Type	Str
h-90b7b77f59	targets	hypothesis	1.00
SNCA	encodes	gene	0.99
Antisense Oligonucleotides	downregulates	drug	0.95
SQSTM1	mediates	entity	0.95
SNCA ASOs	inhibits	drug	0.95
Tunnelling Nanotubes	mediates	process	0.95
38307024	has isolated effects on	paper	0.90
39819742	associated with	paper	0.90
23266198	interacts selectively with	paper	0.90
23266198	acts as	paper	0.90
24338664	are the main cell type presenting aggregates composed of	paper	0.90
23266198	acts as mixed inhibitor of	paper	0.90
30362073	is expressed in	paper	0.90
30362073	is highly expressed in	paper	0.90
30362073	is highly expressed in neuronal cell bodies of	paper	0.90
GBA1	regulates	gene	0.90
VPS35	associated_with	gene	0.90
N-acetyl-l-leucine	downregulates	compound	0.90
LRRK2	associated_with	gene	0.90
35833836	is lower in	paper	0.90
35833836	is lower in	paper	0.90
G2019S LRRK2	exacerbates	protein	0.90
Microglial Autophagy	targets	process	0.90
Microglia	involved_in	cell_type	0.90
UBIQUITIN	interacts_with	entity	0.90
37189833	is one of the hallmarks of	paper	0.90
LAG3	facilitates_transmission_of	gene	0.90
LC3	mediates	entity	0.85
HSC70	interacts_with	protein	0.85
Parkin	interacts_with	protein	0.85
MTK458	mediates	drug	0.85
NOTCH2NLC	promotes	gene	0.85
Chaperone-Mediated Autophagy	targets	process	0.85
VDAC1	interacts_with	gene	0.80
LRRK2	interacts_with	gene	0.80
Complement C3	exacerbates	protein	0.80
GLP-1	ameliorates	protein	0.80
PLK2	regulates	gene	0.80
ESCRT-III	inhibits	entity	0.80
PARKINSON	associated_with	disease	0.80
C3	exacerbates	protein	0.80
PI3K	degrades	pathway	0.80
GBA	interacts_with	gene	0.80
LRRK2	regulates	protein	0.80
PI3K	regulates	pathway	0.80
SNCA	encodes	gene	0.70
ATC161	inhibits	drug	0.70
p62	interacts_with	protein	0.70
macroautophagy	inhibits	process	0.70
gut microbiota	regulates	cell_type	0.70

Targeting Hypotheses (15)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
Synaptic Vesicle Cycle Hijacking: Shared Convergent Mechanis	0.760	neurodegeneration	-
Bacterial Curli Amyloid → Nucleation of α-Synuclein Misfoldi	0.720	neurodegeneration	What are the mechanisms by which gut mic
Ferroptosis Inhibition for α-Synuclein Neuroprotection	0.705	neurodegeneration	Gene expression changes in aging mouse b
Targeting Bacterial Curli Fibrils to Prevent α-Synuclein Cro	0.642	neurodegeneration	What are the mechanisms by which gut mic
Autophagosome-Lysosome Fusion Defects as Primary Driver of α	0.630	neurodegeneration	Gap 006 analysis (archived stub)

LRRK2 Kinase Inhibition Reduces α-Synuclein Spread via Lysos	0.620	neurodegeneration	Test Hypothesis Fixtures
c-Abl Tyrosine Kinase Activation Drives α-Synuclein Phosphor	0.605	neurodegeneration	Legacy Pre-Pipeline Hypothesis Import
Exosomal α-Synuclein as an Interneuronal Propagation Vector	0.595	neurodegeneration	Legacy Pre-Pipeline Hypothesis Import
TFEB Nuclear Translocation Clears α-Synuclein via Autophagy-	0.580	neurodegeneration	Test Preregistration Analysis
Selective c-Abl Inhibition Promotes α-Synuclein Clearance vi	0.580	neurodegeneration	Test Hypothesis Fixtures
AMPK Activation to Restore Autophagy and Clear α-Synuclein A	0.559	neurodegeneration	Does RGS6 upregulation or D2 autorecepto
Cross-Seeding: Gut Microbiome-Derived Bacterial Curli and Fu	0.540	neurodegeneration	How does gut microbiome dysbiosis contri
Gut Barrier Permeability-α-Synuclein Axis Modulation	0.533	neurodegeneration	What are the mechanisms by which gut mic
Microbial Metabolite-Mediated α-Synuclein Disaggregation	0.511	neurodegeneration	What are the mechanisms by which gut mic
GSK3β Inhibition to Prevent α-Synuclein Phosphorylation and	0.429	neurodegeneration	Does RGS6 upregulation or D2 autorecepto

Mentioning Analyses (2)

Scientific analyses that reference this entity

Comparative epigenetic signatures across AD, PD, and ALS

neurodegeneration | 2026-04-16 | 7 hypotheses Top: 0.550

How do synthetic EVs achieve brain-specific targeting while avoiding reticuloend

drug delivery | 2026-04-15 | 0 hypotheses

Experiments (2)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
S-equol-induced ferroptosis mechanism in TNBC cells	exploratory	Triple negative breast cancer	0.900	0.00	TNBC cell lines	proposed	N/A
Gandouling protection against brain injury in Wilson's disease via SIR	validation	Hepatolenticular degeneration	0.900	0.00	TX mice (Wilson's disease mode	proposed	N/A

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year
GPX4 promotes optic nerve regeneration and retinal ganglion cell neuroprotection [PMID:41485051]	Yang M, Bian F, Feng X, Li L, Huang H et	Mol Ther	2026
Extracellular GPX4 impairs antitumor immunity via dendritic ZP3 receptors. [PMID:41494530]	Liu J, Cai X, Lin J, Zhang Z, Zhou Q et	Cell	2026
Aging at the Crossroads of Cuproptosis and Ferroptosis: From Molecular Pathways [PMID:41516398]	Gromadzka G, Tarnacka B, Cieślik M	Int J Mol Sci	2026
Ferroptosis in neurological diseases: moving towards therapeutic intervention. [PMID:41554903]	Tuo QZ, Bush AI, Lei P	Mol Psychiatry	2026
Fin(e)-tuning ferroptosis. [PMID:41576911]	Szylo KJ, Dixon SJ	Mol Cell	2026
GPX4-dependent ferroptosis governs ILC2 homeostasis and colitis progression. [PMID:41663525]	Liu G, Wang Y, Huang H, Wang J, Yang J e	Cell Mol Immunol	2026
A GPX1-OSBPL8 axis mediates noncanonical in vivo ferroptosis and cancer growth s [PMID:41720096]	Xia Z, Yang X, Samovich SN, Tyurina YY,	Cell	2026
The crossroads of inflammation and oxidative stress: A review of the interplay b [PMID:41722697]	Park WH	Pharmacol Res	2026
Ferroptosis in Cerebral Ischemia/Reperfusion Injury: Mechanistic Drivers and The [PMID:41738060]	Song C, Liu Z, Tang J, Huang Y	Neuropsychiatr Dis Treat	2026
Decoding GPX4 regulation in ferroptosis: mechanisms and therapeutic implications [PMID:41826143]	Chen X	Trends Mol Med	2026
Computational examination of magainin-I-KL mediated disruption of E. coli biofil [PMID:41724836]	Vinutha AS, Akshay S, Sree Agash SG, Cha	Archives of microbiology	2026
Montelukast Modulates MPTP-induced Ferroptosis and Neuroinflammation Linked To t [PMID:41712018]	["Jung Yu Jin", "Choi Hyunsu", "Lee Seon	Neuromolecular medicine	2026
The cytoplasmic protein YedX is a potent inhibitor of CsgA amyloid assembly in E [PMID:41581877]	Gurnani B, Jain N	The Journal of biological chem	2026
A fin-loop-like structure in GPX4 underlies neuroprotection from ferroptosis. [PMID:41349546]	Lorenz SM, Wahida A, Bostock MJ, Seibt T	Cell	2026
Hypoxia-inducible factor-1 as targets for neuroprotection : from ferroptosis to [PMID:39466326]	["Changyong Wang", "Shanyu Lv", "Hongyan	Neurological sciences : offici	2025
Gentiopicroside Attenuated Dopaminergic Neurodegeneration via Inhibiting Neuroin [PMID:40256942]	Unknown	Basic & clinical pharmacol	2025
Astragenol alleviates neuroinflammation and improves Parkinson's symptoms throug [PMID:40306495]	["Shengnan Xiao", "Lianmei Liu", "Xuemei	Journal of ethnopharmacology	2025
Schisanhenol Inhibits MPTP/MPP<sup>+</sup>-Induced Ferroptosis in Dopaminergic N [PMID:41460594]	Unknown	Neurochemical research	2025
Carvedilol Confers Neuroprotective Activity Through Modulating Ferroptosis Key P [PMID:41243756]	Unknown	Journal of biochemical and mol	2025
Betulinic acid protects SH-SY5Y cells exposed to lipopolysaccharide and ferrous [PMID:40985323]	Pandey SK, Singh H, Ahmad S, Singh RK	Free radical research	2025

Debates (2)

Multi-agent debates referencing this entity

What are the shared DNA methylation age acceleration and histone modification pa

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

All participants identified brain delivery as a critical barrier, but no mechani

closed · Rounds: 4 · Score: 0.50 · 2026-04-16

Related Research

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

LRRK2 Kinase Inhibition Reduces α-Synuclein Spread via Lysosomal Enhancement

Score: 0.620 · neurodegeneration · 2026-04-26

LRRK2 G2019S gain-of-function mutation hyperactivates kinase activity, dysregulating RAB GTPases and impairing lysosomal

c-Abl Tyrosine Kinase Activation Drives α-Synuclein Phosphorylation and Neurodeg

Score: 0.605 · neurodegeneration · 2026-04-26

c-Abl (ABL1) phosphorylates α-synuclein at Y39, promoting aggregation and neuronal toxicity. Nilotinib (FDA-approved for

Exosomal α-Synuclein as an Interneuronal Propagation Vector in Parkinson's Disea

Score: 0.595 · neurodegeneration · 2026-04-26

Misfolded α-synuclein aggregates are transmitted via exosomes from donor to recipient neurons, templating endogenous aSy

TFEB Nuclear Translocation Clears α-Synuclein via Autophagy-Lysosome Pathway

Score: 0.580 · neurodegeneration · 2026-04-28

Forced nuclear localization of TFEB using AAV9-TFEB(S211A) induces transcription of autophagy-lysosomal genes, enhancing

Selective c-Abl Inhibition Promotes α-Synuclein Clearance via Autophagy

Score: 0.580 · neurodegeneration · 2026-04-26

c-Abl kinase is activated in PD substantia nigra and phosphorylates parkin at Tyr143, inhibiting its E3 ligase activity

AMPK Activation to Restore Autophagy and Clear α-Synuclein Aggregates

Score: 0.559 · neurodegeneration · 2026-04-18

## Mechanistic Overview AMPK Activation to Restore Autophagy and Clear α-Synuclein Aggregates starts from the claim that

Cross-Seeding: Gut Microbiome-Derived Bacterial Curli and Fungal Amyloid Synergi

Score: 0.540 · neurodegeneration · 2026-04-26

Commensal bacteria (E. coli, Salmonella) produce curli amyloid fibers encoded by the csg operon, while Candida and Sacch

Gut Barrier Permeability-α-Synuclein Axis Modulation

Score: 0.533 · neurodegeneration · 2026-04-02

Dysbiotic bacteria compromise intestinal barrier integrity through zonulin pathway activation, allowing bacterial antige

Microbial Metabolite-Mediated α-Synuclein Disaggregation

Score: 0.511 · neurodegeneration · 2026-04-02

Specific gut bacterial strains produce short-chain fatty acids (SCFAs) that cross the blood-brain barrier and directly m

GSK3β Inhibition to Prevent α-Synuclein Phosphorylation and Aggregation

Score: 0.429 · neurodegeneration · 2026-04-18

## Mechanistic Overview GSK3β Inhibition to Prevent α-Synuclein Phosphorylation and Aggregation starts from the claim th