SNCA

Synuclein alpha

Score: 0.605 Price: $0.60 Medium Druggability Status: active Wiki: SNCA

🟢 Parkinson's Disease 🧠 Neurodegeneration

HYPOTHESES

5

PAPERS

18

KG EDGES

1439

DEBATES

1

3D Protein Structure

🧬 SNCA — PDB 1XQ8 Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Medium

Score: 0.49

Clinical Stage

Phase II

Target Class

Structural Protein

Safety

0.30

Druggability Analysis

Drug Development0.40

Structural Tractability0.95

Target Class0.50

Safety Profile0.30

Key Metrics

PDB Structures:

187

Known Drugs:

2

Approved:

0

In Clinical Trials:

2

Drug Pipeline (2 compounds)

1 Phase II · 1 Phase I

Druggability Rationale: SNCA demonstrates high druggability (0.80 score) despite being an intrinsically disordered protein, supported by 187 PDB structures, cryo-EM data, and active clinical programs (Prasinezumab in Phase 2). The extensive structural characterization and successful immunotherapy approaches validate this target's tractability for both monoclonal antibodies targeting aggregates and small molecules preventing pathological conformational transitions.

Mechanism: Immunotherapy targeting alpha-synuclein aggregates or small molecules preventing aggregation

Drug Pipeline (2 compounds)

1 Phase II · 1 Phase I

Known Drugs:

Prasinezumab (phase_2) — Parkinson's disease

Cinpanemab (phase_1) — Parkinson's disease

Structural Data:

PDB (187) ✓AlphaFold ✓Cryo-EM ✓

10XU 1XQ8 2KKW 2N0A 3Q26+182 more

UniProt: P37840

🧬 3D Protein Structure

🧬 SNCA — PDB 1XQ8 Click to expand interactive 3D viewer

Experimental structure from RCSB PDB | Powered by Mol* | Rotate: click+drag | Zoom: scroll

Selectivity & Safety Considerations

Selectivity is minimally challenged as SNCA is a unique gene with limited isoforms, though off-target engagement with beta-synuclein and gamma-synuclein family members must be considered for small molecule approaches. Immunotherapy selectivity is inherently high, targeting pathological aggregates rather than native monomeric forms.

3D Protein Structure

PDB: Open in RCSB AlphaFold model

Interactive 3D viewer powered by RCSB PDB / Mol*. Use mouse to rotate, scroll to zoom.

Clinical Trials (8)

Relevant trials from ClinicalTrials.gov

Active

6

Completed

1

Total Enrollment

1,287

By Phase

EARLY_PHASE1: 1 · NA: 4 · PHASE2: 1 · Unknown: 2

Health in Aging, Neurodegenerative Diseases and Dementias In Ontario Terminated

Unknown NCT05062512 n=250

Neuro-Degenerative Disease, Dementia

Sponsor: Ontario Neurodegeneration Disease Research Initiative | Started: 2021-08-26

Identifying Markers of Disease Subtypes and Disease Progression in the Syndrome of Essential Tremor Enrolling By Invitation

Unknown NCT06349538 n=100

Essential Tremor

Interventions: Clinical examination, blood draw, cerebr

Sponsor: Medical University of Graz | Started: 2024-04-04

Movement Improves Brain Health and Cognition in Parkinson's Disease Recruiting

NA NCT07299279 n=150

Parkinson Disease

Interventions: Aerobic exercise for >_75 minutes/wee

Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS | Started: 2025-06-09

Ambroxol as a Disease-modifying Treatment in GBA-PD Completed

PHASE2 NCT05287503 n=65

Parkinson Disease, GBA Gene Mutation

Interventions: Ambroxol Hydrochloride, Placebo

Sponsor: Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta | Started: 2022-03-09

Understanding Alpha-Synuclein Spread in Parkinson's Disease Through Blood Biomarkers and Neuroimaging Not Yet Recruiting

NA NCT07474779 n=160

Parkinson's Disease (PD), GBA1 Parkinson Disease, REM Sleep Behavior Disorder (iRBD)

Interventions: brain imaging, blood draw, Skin biopsy

Sponsor: University of Pavia | Started: 2026-02

Serum Biomarkers in Parkinson's Disease at Different Stages Recruiting

NA NCT05769699 n=200

Parkinson Disease

Interventions: blood sample

Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS | Started: 2022-02-10

Toward Molecular Profiling of Parkinson's Disease in Easily Accessible Biological Matrices Active Not Recruiting

NA NCT07480187 n=340

Parkinson Disease, Synucleinopathy, Alzheimer Disease

Interventions: biomarkers

Sponsor: Azienda Ospedaliera di Perugia | Started: 2023-05-20

Open-label Study to Evaluate Brain α-Synuclein Deposition Using PET and [18F]MK-0947 in Parkinson's Disease Recruiting

EARLY_PHASE1 NCT07348250 n=22

Parkinson's Disease (PD), Parkinson's Disease, Parkinson's Disease (Disorder)

Interventions: [18F]MK-0947

Sponsor: Invicro | Started: 2025-12-08

Linked Hypotheses (10)

SNCA conformer propagation across PD, DLB, and MSA0.820

Exosomal SNCA Propagation from Lysosome-Compromised Neurons Contains a Distinct Lysosomal Proteome S0.777

SNCA Aggregation Hijacks the Endosomal Sorting Complex Required for Transport (ESCRT) Machinery via 0.690

m6A Hypermethylation of SNCA mRNA Stabilises Alpha-Synuclein Transcript and Promotes Lewy Pathology0.662

Alpha-synuclein phosphorylation-dominated LLPS hijacks synaptic vesicle condensates driving Parkinso0.657

Physiological SCFAs may reduce alpha-synuclein burden primarily through a gut-first or ENS-first mec0.650

early PD proteogenomic hubs that are both causal enough and accessible enough to perturb as proximal0.626

Neuronal Subtype-Specific Alpha-Synuclein Expression Normalization0.571

Sulfated glycans and metal-binding CSF proteins brace alpha-synuclein fibril polymorphs0.489

H2S/butyrate imbalance drives enteric alpha-synuclein pathology via TLR4 signaling0.380

Linked Experiments (5)

Long-term perampanel treatment in A53T BAC-SNCA mice with PFF injection0.950

PFF uptake in primary hippocampal neurons with inhibitors0.900

Dexamethasone treatment study in α-synuclein mice0.850

PFF clearance kinetics in Snca knockout mice0.800

Individuals with SNCA pathogenic variants reported painful dystonia, lower extremity pain, dorsal pa0.500

Scoring Dimensions

Knowledge Graph (20)

co discussed (12)

FOXP3→SNCATNFA→SNCAPPARGC1A→SNCAPRKAA1→SNCANR3C1→SNCA

▸ Show 7 more

CHR2→SNCACLOCK→SNCACRH→SNCABDNF→SNCASNCA→ANGPT1SNCA→ULK1SNCA→PDGFRB

encodes (1)

SNCA→alpha_synuclein

interacts with (7)

DRD2→SNCASNCA→DRD2SNCA→HSPA1ASNCA→DNMT1HSPA1A→SNCA

▸ Show 2 more

DNMT1→SNCATLR4→SNCA

Debate History (1)

Should SNCA (Synuclein alpha) be prioritized as a therapeutic target for neurode2026-04-21