Sarm1, short for sterile alpha and TIR motif-containing 1, is a key mediator in both the immune and nervous systems. It functions as a nicotinamide adenine dinucleotide (NAD+)-cleaving enzyme. Its activation is associated with axon degeneration, and it also plays roles in pathways like NF-κB signaling. Genetic models, such as knockout and conditional knockout mice, have been crucial for studying Sarm1's functions [2,3,6].

In spinal cord injury (SCI) mouse models, conditional knockout (CKO) of Sarm1 in the central nervous system (CNS) using Nestin-Cre and GFAP-Cre transgenic mice crossed with Sarm1flox/flox mice promoted neuronal regeneration and functional recovery. This was achieved through reduced neuroinflammation at the early phase of SCI via down-regulation of NF-κB signaling, potentially due to up-regulation of HSP70 [1].

In Alzheimer's disease (AD) model mice, CKO of Sarm1 in the CNS (Sarm1Nestin-CKO mice) delayed cognitive decline, reduced Aβ deposition, and inhibited neurodegeneration by down-regulating TNF-α signaling [4].

In paclitaxel-induced peripheral neuropathy, Sarm1 knockout mice showed prevention of loss of axonal function in a gene-dosage-dependent manner, and pharmacological inhibition of Sarm1 protected axon structure and function [5].

In conclusion, Sarm1 is a significant factor in axon degeneration and neuroinflammation. Studies using Sarm1 KO/CKO mouse models have revealed its roles in diseases like spinal cord injury, Alzheimer's disease, and peripheral neuropathy, suggesting that targeting Sarm1 could be a viable therapeutic approach for these neurological conditions.