Urolithin A improves Alzheimer's disease cognition and restores mitophagy and lysosomal functions.

ABSTRACT:

Background

Compromised autophagy, including impaired mitophagy and lysosomal function, plays pivotal roles in Alzheimer's disease (AD). Urolithin A (UA) is a gut microbial metabolite of ellagic acid that stimulates mitophagy. The effects of UA's long-term treatment of AD and mechanisms of action are unknown.

Methods

We addressed these questions in three mouse models of AD with behavioral, electrophysiological, biochemical, and bioinformatic approaches.

Results

Long-term UA treatment significantly improved learning, memory, and olfactory function in different AD transgenic mice. UA also reduced amyloid beta (Aβ) and tau pathologies and enhanced long-term potentiation. UA induced mitophagy via increasing lysosomal functions. UA improved cellular lysosomal function and n

SUBMITTER: Hou Y 

PROVIDER: S-EPMC11180933 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature