Nicotinamide Riboside Provides Benefit in Amyotrophic Lateral Sclerosis: Preclinical Findings

Synopsis

This study explores how boosting nicotinamide adenine dinucleotide (NAD+) metabolism in astrocytes can protect neurons from degeneration in amyotrophic lateral sclerosis (ALS). NAD+ is vital for mitochondrial energy production and cellular repair but is depleted by certain signaling enzymes. Cells replenish it through the NAD+ salvage pathway, driven by the enzyme nicotinamide phosphoribosyltransferase (NAMPT). Researchers found that enhancing NAD+ synthesis—either by overexpressing NAMPT or supplementing with NAD+ precursors nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR)—increased total and mitochondrial NAD+ in astrocytes. In ALS models with mutant superoxide dismutase 1 (SOD1), this intervention reduced oxidative stress and protected motor neurons from astrocyte-induced toxicity. These findings suggest that restoring NAD+ metabolism in astrocytes may offer a promising therapeutic strategy to slow or prevent motor neuron death in ALS.

Journal

Journal of Biological Chemistry