Dopaminergic neurons with lysosomal stress (either from GBA1 mutations, VPS35 dysfunction, or age-related LAMP2A decline) release exosomes enriched in SNCA via a mechanism involving CD63 and syntenin-mediated exosome biogenesis at multivesicular bodies (MVBs). Critically, these exosomes carry a distinct cargo signature reflecting their lysosomal origin: they are enriched in mature cathepsins (particularly cathepsin D in its active form), LAMP1 fragments, and glucosylceramide. When these exosomes
Radar Chart — 10 Dimensions
Score Comparison Bars
Mechanistic
0.78
Evidence
0.70
Novelty
0.85
Feasibility
0.00
Impact
0.00
Druggability
0.00
Safety
0.00
Competition
0.00
Data
0.00
Reproducible
0.00
KG Connect
0.35
Score Breakdown
Dimension
Exosomal SNCA Propagation from
Mechanistic
0.780
Evidence
0.700
Novelty
0.850
Feasibility
0.000
Impact
0.000
Druggability
0.000
Safety
0.000
Competition
0.000
Data
0.000
Reproducible
0.000
KG Connect
0.353
Evidence
Exosomal SNCA Propagation from Lysosome-Compromised Neurons