Aerobic Exercise Attenuates Autophagy-Lysosomal Flux Deficits via β2-AR-Mediated ESCRT-III Subunit CHMP4B in Mice With Human MAPT P301L.

ABSTRACT: Deficits in the autophagy-lysosomal pathway facilitate intracellular microtubule associated protein tau (MAPT) accumulation in Alzheimer disease (AD). Aerobic exercise (AE) has been recommended as a way to delay and treat AD, but the exact effects and mechanisms have not been fully elucidated. Here, we found that AE (8-week treadmill running, 40 min/day, 5 days/week) alleviated autophagy-lysosomal defects and MAPT pathology through the activation of β2-adrenergic receptors (β2-AR) in MAPT P301L mice. Molecular mechanistic investigations revealed that endosomal sorting complex required for transport (ESCRT) III subunit charged multivesicular body protein 4B (CHMP4B), which is essential for autophagosome-lysosome fusion, was significantly decreased in the cerebral cortex of AD patients and t

SUBMITTER: Bi SG 

PROVIDER: S-EPMC12507411 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature