Mitophagy Enhancers, Including Nicotinamide Riboside, Are Protective in Alzheimer's Disease: Preclinical Findings

Synopsis

This study examines whether mitophagy enhancers can protect brain cells from the harmful effects of mutant APP and amyloid beta (Aβ) in Alzheimer’s disease (AD). Since mitochondrial dysfunction and poor clearance of damaged mitochondria are early events in AD, we tested four enhancers—urolithin A, actinonin, tomatidine, and nicotinamide riboside—in mouse hippocampal (HT22) neurons expressing mutant APP. Mutant cells showed mitochondrial fragmentation, reduced fusion, lower expression of synaptic and mitophagy genes, and decreased survival. Treatment with mitophagy enhancers reversed these effects, restoring mitochondrial health and improving cell survival. Among them, urolithin A showed the strongest protective effects, suggesting that mitophagy enhancers may be promising therapeutic candidates for Alzheimer’s disease.

Journal

Human Molecular Genetics