AUTHOR=Wang Chenfei , Huang Wei , Lu Jia , Chen Hongzhuan , Yu Zhihua 

TITLE=TRPV1-Mediated Microglial Autophagy Attenuates Alzheimer’s Disease-Associated Pathology and Cognitive Decline

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 12 - 2021

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.763866

DOI=10.3389/fphar.2021.763866

ISSN=1663-9812

ABSTRACT=Autophagy is a major regulator of the ageing process of the central nervous system and neurodegeneration. Autophagy dysfunction has been implicated in the pathogenesis of Alzheimer’s disease (AD). TRPV1 was reported to regulate autophagy to protect against foam cell formation and reduce the release of inflammatory factors in atherosclerosis. In this study, pharmacological activation of TRPV1 with the TRPV1 agonist capsaicin induced autophagy in primary microglia in a TRPV1-dependent manner. TRPV1-mediated autophagy regulated glycolysis and oxidative phosphorylation in microglia by controlling the expression of genes required for aerobic glycolysis and mitochondrial respiration. TRPV1 agonist capsaicin decreased amyloid and phosphorated tau pathology and reversed memory deficits by promoting microglia activation, metabolism and autophagy in 3xTg mice. These results indicate that TRPV1 was a potential therapeutic target for AD, which suggests that capsaicin should be further assessed as a possible treatment for AD.