Inhibiting CD38 and Boosting NAD+ with Nicotinamide Riboside Reduces Brain Inflammation: Preclinical Findings

Synopsis

Neuroinflammation begins when the brain's innate immune system responds to inflammation. If not properly controlled, this inflammation worsens diseases like multiple sclerosis and Alzheimer's. NAD+ is important for energy production and calcium balance in cells. Previous research showed that removing CD38, an enzyme that uses NAD+, reduces brain inflammation and damage. However, it was unclear if CD38 affects neuroinflammation by changing brain NAD+ levels. This study examined how deleting or blocking CD38, and increasing NAD+ with nicotinamide riboside (NR), affects inflammation caused by lipopolysaccharide (LPS) in mice. LPS increased CD38 levels, especially in the hippocampus. Mice without CD38 showed less inflammation and glial cell activation. Giving mice apigenin (a CD38 inhibitor) or NR raised NAD+ levels and strongly reduced inflammatory molecules, glial activation, and nerve cell damage after LPS treatment. In cell studies, apigenin, NAD+, NR, and a specific CD38 inhibitor (78c) lowered inflammation in astrocytes and microglia by blocking the NF-κB pathway. These findings suggest that CD38-driven inflammation is linked to NAD+ use, and that increasing NAD+ by inhibiting CD38 or giving NR can directly reduce brain inflammation.

Journal

Journal of Neurochemistry