concept

SYNUCLEIN

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about 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.

518Connections

30Hypotheses

0Analyses

46Outgoing

50Incoming

2Experiments

0Debates

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💡 Concept Info

Name	SYNUCLEIN
Key Genes/Proteins	ABCD3, ACTB, AIF1, AKT, Alpha-Synuclein, ALZHEIMER
Related Diseases	acetylcholine, aging, alpha-synucleinopathies, ALS, Alzheimer Disease

Wiki Pages (1)

Knowledge base pages for this entity

Canonical Page

AbSci (Zero-Shot Antibody Design)

ai_tool · 455 words

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Pathway Diagram

graph TD
    SYNUCLEIN["SYNUCLEIN"]
    PARKINSON_S_DISEASE["PARKINSON'S DISEASE"] -->|"causes"| SYNUCLEIN
    AUTOPHAGY["AUTOPHAGY"] -->|"activates"| SYNUCLEIN
    P62["P62"] -->|"activates"| SYNUCLEIN
    SQSTM1["SQSTM1"] -->|"activates"| SYNUCLEIN
    MICROGLIA["MICROGLIA"] -->|"inhibits"| SYNUCLEIN
    ASTROCYTES["ASTROCYTES"] -->|"activates"| SYNUCLEIN
    ALS["ALS"] -->|"activates"| SYNUCLEIN
    AMPK["AMPK"] -->|"activates"| SYNUCLEIN

Outgoing (46)

Target	Relation	Type	Str
Proteins	interacts_with	protein	0.50
AMYLOID-β	interacts_with	concept	0.50
α-SYNUCLEIN	interacts_with	concept	0.50
α-SYNUCLEIN	inhibits	concept	0.50
α-SYNUCLEIN	associated_with	concept	0.50
DOPAMINERGIC NEURONS	interacts_with	concept	0.50
RAPAMYCIN	interacts_with	concept	0.50
CENTRAL NERVOUS SYSTEM	interacts_with	concept	0.50
Proteins	activates	protein	0.50
Proteins	inhibits	protein	0.50
LEWY BODY	inhibits	concept	0.50
Gut Microbiota	associated_with	process	0.50
DOPAMINERGIC NEURONS	associated_with	concept	0.50
LEWY BODY	interacts_with	concept	0.50
Proteins	regulates	protein	0.50
GLIOSIS	inhibits	concept	0.50
MICROGLIAL ACTIVATION	activates	concept	0.50
SELECTIVE AUTOPHAGY	decreases_risk	concept	0.50
Proteins	associated_with	protein	0.50
PI3K/AKT/mTOR	activates	pathway	0.50
Proteins	expressed_in	protein	0.50
NEUROFIBRILLARY TANGLES	expressed_in	concept	0.50
LEWY BODY	activates	concept	0.50
α-SYNUCLEIN	decreases_risk	concept	0.50
AMYLOID-β	associated_with	concept	0.50
HCRT	regulates	concept	0.50
DOPAMINERGIC NEURONS	regulates	concept	0.50
Reactive Oxygen Species	activates	process	0.50
NUCLEUS	activates	concept	0.50
ENDOPLASMIC RETICULUM	activates	concept	0.50
DOPAMINE	associated_with	concept	0.50
DOPAMINE	causes	concept	0.50
α-SYNUCLEIN	causes	concept	0.50
DOPAMINE	activates	concept	0.50
α-SYNUCLEIN	activates	concept	0.50
DOPAMINE	inhibits	concept	0.50
DOPAMINE	regulates	concept	0.50
α-SYNUCLEIN	regulates	concept	0.50
LEWY BODY	associated_with	concept	0.50
LEWY BODY	expressed_in	concept	0.50
DOPAMINERGIC NEURONS	inhibits	concept	0.50
α-SYNUCLEIN	expressed_in	concept	0.50
DOPAMINERGIC NEURONS	causes	concept	0.50
Reactive Oxygen Species	causes	process	0.50
RAPAMYCIN	activates	concept	0.50
NEUROFIBRILLARY TANGLES	associated_with	concept	0.50

Incoming (472)

Source	Relation	Type	Str
TAU	associated_with	protein	1.00
MICROGLIA	associated_with	cell_type	1.00
ASTROCYTES	associated_with	cell_type	1.00
AMYLOID	associated_with	protein	1.00
ALZHEIMER'S DISEASE	associated_with	disease	1.00
PARKINSON'S DISEASE	associated_with	disease	1.00
UBIQUITIN	associated_with	protein	0.98
PARKINSON'S DISEASE	causes	disease	0.98
P62	associated_with	protein	0.98
PARKINSON'S DISEASE	activates	disease	0.90
IL-6	associated_with	gene	0.90
LRRK2	associated_with	gene	0.82
SOD1	associated_with	gene	0.82
NF-KB	associated_with	protein	0.82
PINK1	associated_with	gene	0.82
PARKIN	associated_with	gene	0.82
TARDBP	associated_with	gene	0.82
ALS	associated_with	disease	0.82
PARKINSON'S DISEASE	regulates	disease	0.74
TAU	interacts_with	protein	0.74
AMYLOID	interacts_with	protein	0.74
TNF	associated_with	gene	0.74
MTOR	associated_with	gene	0.74
APOE	associated_with	gene	0.66
NRF2	associated_with	gene	0.66
PARKIN	causes	gene	0.66
AKT	associated_with	gene	0.66
PI3K	associated_with	gene	0.66
SQSTM1	associated_with	gene	0.66
MICROGLIA	activates	cell_type	0.64
MTOR	activates	gene	0.56
AMYLOID	activates	protein	0.56
CASP3	associated_with	gene	0.56
P62	activates	protein	0.56
TAU	activates	protein	0.56
TAU	phosphorylates	protein	0.56
SQSTM1	activates	gene	0.56
ASTROCYTES	activates	cell_type	0.56
PARKINSON'S DISEASE	interacts_with	disease	0.56
PARKINSON'S DISEASE	mediates	disease	0.56
MICROGLIA	inhibits	cell_type	0.56
LRRK2	activates	gene	0.56
CNTNAP4	regulates	gene	0.50
Substantia Nigra	associated_with	entity	0.50
Neurodegenerative Diseases	interacts_with	disease	0.50
CHOP	activates	gene	0.50
CALCOCO2	activates	gene	0.50
FIP200	activates	gene	0.50
PRESENILIN	activates	protein	0.50
ALZHEIMER	interacts_with	gene	0.50

Targeting Hypotheses (30)

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
Synaptic Vesicle Cycle Hijacking: Shared Convergent Mechanis	0.760	neurodegeneration	-
LAMP2A-Mediated Autophagy Enhancement Blocks Alpha-Synuclein	0.745	neurodegeneration	Test
Pharmacologic activation of GBA1 to reduce alpha-synuclein b	0.720	neurodegeneration	Test

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
A downstream LRRK2-Rab10-JIP4 lysosomal stress loop promotes	0.680	neurodegeneration	Do pathogenic LRRK2 mutations amplify vo
Physiological SCFAs may confer indirect anti-synuclein benef	0.670	neurodegeneration	Do physiological concentrations of SCFAs
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	-
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)
m6A-dependent control of alpha-synuclein transcript fate and	0.626	neurodegeneration	m6A RNA Modification and Alpha-Synuclein
LRRK2 Kinase Inhibition Reduces α-Synuclein Spread via Lysos	0.620	neurodegeneration	Test Hypothesis Fixtures
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
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
Ganglioside-rich extracellular vesicles preserve alpha-synuc	0.582	neurodegeneration	Which specific CSF molecular components
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
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
AMPK Activation to Restore Autophagy and Clear α-Synuclein A	0.559	neurodegeneration	Does RGS6 upregulation or D2 autorecepto
Physiological SCFAs may worsen alpha-synuclein pathology thr	0.550	neurodegeneration	Do physiological concentrations of SCFAs

Mentioning Analyses (0)

Scientific analyses that reference this entity

No analyses mention this entity

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
Montelukast Modulates MPTP-induced Ferroptosis and Neuroinflammation Linked To t [PMID:41712018]	["Jung Yu Jin", "Choi Hyunsu", "Lee Seon	Neuromolecular medicine	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
Neuroprotective role of CHCHD2 in Parkinson's disease: Insights into the GPX4-re [PMID:39566750]	["Wang Fang", "Liu Xuanzhuo", "Chen Ming	Free radical biology & medicin	2025
Granulathiazole A protects 6-OHDA-induced Parkinson's disease from ferroptosis v [PMID:38678778]	Unknown	Bioorganic chemistry	2024

Debates (0)

Multi-agent debates referencing this entity

No debates reference this entity

Related Research

Hypotheses and analyses mentioning SYNUCLEIN in their description or question text

Bacterial Curli Amyloid → Nucleation of α-Synuclein Misfolding in Enteric Neuron

Score: 0.720 · neurodegeneration · 2026-04-22

**Molecular Mechanism and Rationale** The molecular basis of this hypothesis centers on the structural and biochemical

Ferroptosis Inhibition for α-Synuclein Neuroprotection

Score: 0.705 · neurodegeneration · 2026-04-04

## Molecular Mechanism and Rationale Ferroptosis represents a distinct form of regulated cell death characterized by ir

A downstream LRRK2-Rab10-JIP4 lysosomal stress loop promotes alpha-synuclein rel

Score: 0.680 · neurodegeneration · 2026-04-24

Even if G2019S mainly elevates the kinase floor, that increase may still become pathogenic by pushing a thresholded down

Physiological SCFAs may confer indirect anti-synuclein benefit through an entero

Score: 0.670 · neurodegeneration · 2026-04-24

At realistic exposure levels, SCFAs are more likely to act as receptor-mediated endocrine signals than as direct neurona

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

Targeting Bacterial Curli Fibrils to Prevent α-Synuclein Cross-Seeding

Score: 0.642 · neurodegeneration · 2026-04-02

## Mechanistic Overview Targeting Bacterial Curli Fibrils to Prevent α-Synuclein Cross-Seeding starts from the claim tha

Autophagosome-Lysosome Fusion Defects as Primary Driver of α-Synuclein Propagati

Score: 0.630 · neurodegeneration · 2026-04-22

## **Molecular Mechanism and Rationale** The autophagosome-lysosome fusion process represents a critical checkpoint in

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

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

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