REV-ERBα regulates brain NAD⁺ levels and tauopathy via an NFIL3-CD38 axis.

ABSTRACT: Nicotinamide adenine dinucleotide (NAD⁺) is a critical metabolic co-enzyme implicated in brain aging, and augmenting NAD⁺ levels in the aging brain is an attractive therapeutic strategy for neurodegeneration. However, the molecular mechanisms of brain NAD⁺ regulation are incompletely understood. In cardiac tissue, the circadian nuclear receptor REV-ERBα has been shown to regulate NAD⁺ via control of the NAD⁺-producing enzyme NAMPT. Here we show that REV-ERBα controls brain NAD⁺ levels through a distinct pathway involving NFIL3-dependent suppression of the NAD⁺-consuming enzyme CD38, particularly in astrocytes. REV-ERBα deletion does not affect NAMPT expression in the brain and has an opposite effect on NAD^+</

SUBMITTER: Lee J 

PROVIDER: S-EPMC12532575 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature