NAD⁺ Reduction in Glutamatergic Neurons Induces Lipid Catabolism and Neuroinflammation in the Brain via SARM1.

ABSTRACT: NAD⁺ homeostasis is vital for neuronal health, as demonstrated by the opposing roles of nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2), a NAD⁺-synthesizing enzyme, and sterile alpha and TIR motif-containing protein 1 (SARM1), a NAD⁺ hydrolase. Neurodegenerative insults that decrease NMNAT2 activate SARM1, leading to axon loss. To understand how the NMNAT2-SARM1 axis influences brain energy metabolism, multi-omics approaches are used to investigate the metabolic changes resulting from neuronal NMNAT2 loss. Loss of NMNAT2 in glutamatergic neurons leads to a significant metabolic shift in the cerebral cortex from glucose to lipid catabolism, reduced lipid abundance, and pronounced neurodegenerative phenotypes and motor behavioral deficits. These metabolic disturbances are accompan

SUBMITTER: Niou ZX 

PROVIDER: S-EPMC12866834 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature