Capsaicin Alleviates Autophagy-Lysosomal Dysfunction via PPARA-Mediated V-ATPase Subunit ATP6V0E1 Signaling in 3xTg-AD Mice.

ABSTRACT: Autophagy-lysosomal pathway deficits contribute to the accumulation of amyloid-β (Aβ), Tau, and lipid droplets in Alzheimer's disease (AD). Capsaicin, a specific agonist of transient receptor potential vanilloid 1 (TRPV1), can improve cognitive function in AD patients, but the detailed mechanism is still unclear. Here, it is revealed that capsaicin ameliorated AD-related pathology by activating peroxisome proliferator-activated receptor alpha (PPARA/PPARα, a key regulator of lipid metabolism) to promote lipid metabolism and reverse autophagy-lysosomal deficits. Molecular mechanism research found that capsaicin significantly activated the PPAR signaling pathway to promote lipid metabolism, with PPARA identified as the key transcription factor. In addition, capsaicin upregulated ATP6V0E1 (V-

SUBMITTER: Yu H 

PROVIDER: S-EPMC12533174 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature