Mechanism of initiation and regulation of axonal degeneration with special reference to NMNATs and Sarm1

Axonal degeneration is observed in a variety of contexts in both the central and peripheral nervous systems. Pathological signaling to regulate the progression of axonal degeneration has long been studied using Wallerian degeneration, the prototypical axonal degradation observed after injury, as a representative model. Understanding metabolism of nicotinamide adenine dinucleotide (NAD+) and the functional regulation of Sarm1 has generated great progress in this field, but there are a number of remaining questions. Here, in this short review, we describe our current understanding of the axonal degeneration mechanism, with special reference to the biology related to wlds mice and Sarm1. Furthermore, variations of axonal degeneration initiation are discussed in order to address the remaining questions needed for mechanistic clarification.