Chronically Low NMNAT2 Expression Causes Sub-lethal SARM1 Activation and Altered Response to Nicotinamide Riboside in Axons.

ABSTRACT: Nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) is an endogenous axon survival factor that maintains axon health by blocking activation of the downstream pro-degenerative protein SARM1 (sterile alpha and TIR motif containing protein 1). While complete absence of NMNAT2 in mice results in extensive axon truncation and perinatal lethality, the removal of SARM1 completely rescues these phenotypes. Reduced levels of NMNAT2 can be compatible with life; however, they compromise axon development and survival. Mice born expressing sub-heterozygous levels of NMNAT2 remain overtly normal into old age but develop axonal defects in vivo and in vitro as well as behavioural phenotypes. Therefore, it is important to examine the effects of constitutively low NMNAT2 expression on SARM1 activatio

SUBMITTER: Antoniou C 

PROVIDER: S-EPMC11790816 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature