Fig. 5: Aspirin mediates the degradation of α-syn aggregates through a K63 ubiquitination-dependent endosomal pathway.

K63 ubiquitination is the key signaling mediator for the degradation of α-syn aggregates in primary neurons (a) and H4 cells (b). Shown are representative western blot (top) and corresponding quantitative results (bottom). The overexpression of K63R ubiquitin variant in both primary neurons and H4 cells diminishes the aspirin-induced clearance of α-syn aggregates (n = 3 independent experiments, One-way ANOVA with Tukey’s multiple comparisons test, data presented as mean ± SEM). c Aspirin induces K63-linked ubiquitination on α-syn. Ubiquitinated proteins were immunoprecipitated using an anti-myc pull-down, and α-syn levels were measured by mass spectrometry (n = 3 independent experiments, unpaired two-tailed t-test, data presented as mean ± SEM). Source data are provided as a Source Data file.