Convergence hypothesis: Both α-synuclein (SNCA) in Parkinson's disease and tau (MAPT) in Alzheimer's disease exploit the same synaptic vesicle cycle machinery for trans-synaptic propagation, making the vesicle trafficking pathway a shared therapeutic target.
PD-specific mechanism: α-synuclein binds to synaptic vesicles (SYP, SV2A, SYNPR) at the presynaptic terminal, inducing conformational conversion of endogenous α-synuclein into β-sheet-rich oligomers. These oligomers traffic in both directions across the synapse via activity-dependent exo/endocytosis, explaining the stereotypical pattern of Lewy body spreading (Braak stages I-VI).
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Curated pathway diagram from expert analysis
flowchart TD
A["Presynaptic Vesicle Cycle
SNAP25 VAMP2 DNM1"]
B["SNCA Vesicle Binding
Conformational Conversion"]
C["MAPT Tau Seed Uptake
Endocytic Synaptic Entry"]
D["CAV1 and Endosome Sorting
Shared Trafficking Hub"]
E["Exocytosis and Reuptake Loop
Trans Synaptic Transfer"]
F["PD and AD Propagation Convergence
SNCA Tau Spread"]
G["Vesicle Cycle Intervention
Shared Therapeutic Target"]
A --> B
A --> C
B --> D
C --> D
D --> E
E --> F
G -.->|"targets"| A
style A fill:#1a237e,stroke:#4fc3f7,color:#4fc3f7
style F fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9a
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No clinical trials data available
Freshness score = exp(-age×ln2/5): halves every 5 years. Green >0.6, Amber 0.3–0.6, Red <0.3.
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No DepMap CRISPR Chronos data found for SNCA,MAPT,SNAP25,DNM1,VAMP2,CAV1.
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