Nicotinamide Riboside Restores NAD+ and Improves Survival of Neurons with Autophagy Defects: Preclinical Findings

Synopsis

Autophagy is a cellular recycling process vital for neuron survival, and its failure contributes to neurodegenerative diseases. This study generated human neurons lacking the autophagy gene ATG5 and found they showed metabolic defects and increased cell death. Loss of autophagy caused hyperactivation of NAD-consuming enzymes, leading to depletion of NAD+ and mitochondrial dysfunction. Importantly, boosting NAD+ levels with precursors restored mitochondrial function and improved neuron survival. These results reveal a mechanistic link between autophagy failure and NAD+ loss, identifying NAD+ restoration as a potential therapeutic strategy for diseases involving autophagy defects.

Journal

Cell Reports