m6A-dependent control of alpha-synuclein transcript fate and aggregation kinetics should produce a measurable proximal phenotype before late disease pathology. The decisive test is dopaminergic-neuron perturbation of m6A writers/erasers/readers with RNA stability, translation, and Lewy-body-like aggregation assays.
Curated pathway from expert analysis
flowchart TD
A["METTL3/METTL14 Complex<br/>m6A Writer Activity on SNCA Transcripts"]
B["YTHDF1/DF2/DF3 Recognition<br/>m6A Modification at 3UTR and CDS"]
C["SNCA mRNA Stability Modulation<br/>Translation Efficiency Altered"]
D["pSer129-SNCA Aggregation<br/>Hyperphosphorylated Alpha-Synuclein Accumulation"]
E["Lewy Body Formation<br/>Intraneuronal Protein Aggregation"]
F["PD Neurodegeneration<br/>Dopaminergic Neuron Loss in Substantia Nigra"]
A --> B
B --> C
C --> D
D --> E
E --> F
style A fill:#4a148c,stroke:#ce93d8,color:#ce93d8
style F fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9aNo linked papers recorded for this hypothesis yet.
No curated PDB or AlphaFold mapping for M6A yet. Search RCSB →
No clinical trials data linked to this hypothesis yet.
No curated ClinVar variants loaded for this hypothesis.
Run scripts/backfill_clinvar_variants.py to fetch P/LP/VUS variants.
No DepMap CRISPR Chronos data found for m6A.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.