Disrupted NAD+ Metabolism Leads to Brain Defects in Zika Virus-Linked Microcephaly: Preclinical Findings

Synopsis

Zika virus (ZIKV) infection during pregnancy can cause microcephaly, a condition where babies are born with abnormally small brains. In this study, researchers analyzed infected mouse brains using advanced “multi-omics” techniques to understand how the virus disrupts metabolism. They found that Zika infection causes major disturbances in NAD-related pathways, including oxidative phosphorylation, the TCA cycle, and tryptophan metabolism, all of which are essential for brain growth and energy production. When researchers boosted NAD+ levels using nicotinamide riboside (NR)—a vitamin B3 derivative—it significantly reduced brain cell death, increased cortical thickness, and improved survival and brain weight in infected mice. These findings suggest that NAD+ restoration with NR supplementation can help counteract Zika-induced brain damage, providing a promising new direction for preventing virus-related developmental disorders.

Journal

Nature Metabolism