The NAD⁺ precursor NMN activates dSarm to trigger axon degeneration in Drosophila.

ABSTRACT: Axon degeneration contributes to the disruption of neuronal circuit function in diseased and injured nervous systems. Severed axons degenerate following the activation of an evolutionarily conserved signaling pathway, which culminates in the activation of SARM1 in mammals to execute the pathological depletion of the metabolite NAD⁺. SARM1 NADase activity is activated by the NAD⁺ precursor nicotinamide mononucleotide (NMN). In mammals, keeping NMN levels low potently preserves axons after injury. However, it remains unclear whether NMN is also a key mediator of axon degeneration and dSarm activation in flies. Here, we demonstrate that lowering NMN levels in Drosophila through the expression of a newly generated prokaryotic NMN-Deamidase (NMN-D) preserves severed

SUBMITTER: Llobet Rosell A 

PROVIDER: S-EPMC9788811 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature