Nicotinamide Riboside Improves Survival and Motor Function in Parkinson’s Disease: Preclinical Findings

Synopsis

Parkinson’s disease (PD) is a neurodegenerative disorder marked by the loss of dopamine-producing neurons, leading to motor dysfunction and other symptoms. This study investigated how nicotinamide riboside (NR)—a vitamin B3–derived NAD+ precursor—protects against Parkinson’s-related nerve damage in a zebrafish model exposed to the neurotoxin MPTP. NR treatment improved movement, survival, and neuron health, while restoring NAD+ levels. Genetic and metabolic analyses revealed that NR rebalanced glucose metabolism, increasing glycolytic enzyme activity and glucose availability, and raised levels of key metabolic compounds like nicotinamide, nicotinic acid, and glutamine. NR also reduced endoplasmic reticulum stress (ERS)—a major contributor to neuron death—by regulating the Perk–Eif2α–Atf4–Chop signaling pathway. Together, these findings show that NR protects dopamine neurons and improves energy metabolism by easing ER stress, offering valuable insights into its potential as a neuroprotective therapy for Parkinson’s disease.

Journal

Chemico-Biological Interactions