Mitophagy Enhancers, Including Nicotinamide Riboside, Protect Neurons from Tau-Induced Damage in Alzheimer’s Disease: Preclinical Findings

Synopsis

In Alzheimer’s disease (AD), abnormal tau proteins damage mitochondria and synapses, leading to impaired energy production and neuron loss. In mouse hippocampal neurons expressing mutant tau, mitochondrial fission increased, fusion decreased, and genes supporting mitochondrial function, synapses, and mitophagy were reduced, resulting in lower cell survival and defective mitochondrial respiration. Treatment with mitophagy enhancers—including nicotinamide riboside, urolithin A, actinonin, and tomatidine—reversed these effects, improving cell survival, restoring mitochondrial and synaptic gene expression, and reducing mitochondrial fragmentation. Among the compounds tested, urolithin A showed the strongest effect, and combinations with EGCG were even more protective. These findings suggest that mitophagy enhancers are promising strategies to protect neurons and support mitochondrial health in AD.

Journal

Pharmacological Research