Protective effects of NAMPT or MAPK inhibitors and NaR on Wallerian degeneration of mammalian axons.

ABSTRACT: Wallerian degeneration (WD) is a conserved axonal self-destruction program implicated in several neurological diseases. WD is driven by the degradation of the NAD⁺ synthesizing enzyme NMNAT2, the buildup of its substrate NMN, and the activation of the NAD⁺ degrading SARM1, eventually leading to axonal fragmentation. The regulation and amenability of these events to therapeutic interventions remain unclear. Here we explored pharmacological strategies that modulate NMN and NAD⁺ metabolism, namely the inhibition of the NMN-synthesizing enzyme NAMPT, activation of the nicotinic acid riboside (NaR) salvage pathway and inhibition of the NMNAT2-degrading DLK MAPK pathway in an axotomy model in vitro. Results show that NAMPT and DLK inhibition cause a significant b

SUBMITTER: Alexandris AS 

PROVIDER: S-EPMC10621467 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature