The ESCRT machinery (particularly CHMP2B, TSG101, and ALIX) normally mediates budding of intraluminal vesicles into MVBs and resealing of damaged lysosomal membranes. In PD, phosphorylated SNCA (at Ser129) acts as a pathological ligand that recruits ESCRT-III components to lysosomal membranes via a novel phospho-dependent interaction with CHMP2B. Normally, LAMP2A coordinates this process by recruiting TSG101; however, in PD, hyperphosphorylated SNCA outcompetes LAMP2A for TSG101 binding. This re
Radar Chart — 10 Dimensions
Score Comparison Bars
Mechanistic
0.75
Evidence
0.72
Novelty
0.78
Feasibility
0.80
Impact
0.76
Druggability
0.00
Safety
0.00
Competition
0.00
Data
0.00
Reproducible
0.50
KG Connect
0.35
Score Breakdown
Dimension
SNCA Aggregation Hijacks the E
Mechanistic
0.750
Evidence
0.720
Novelty
0.780
Feasibility
0.800
Impact
0.760
Druggability
0.000
Safety
0.000
Competition
0.000
Data
0.000
Reproducible
0.500
KG Connect
0.353
Evidence
SNCA Aggregation Hijacks the Endosomal Sorting Complex Requi