The Drama of Wallerian Degeneration: The Cast, Crew, and Script

Significant advances have been made in recent years in identifying the genetic components of Wallerian degeneration, the process that brings the progressive destruction and removal of injured axons. It has now been accepted that Wallerian degeneration is an active and dynamic cellular process that is well regulated at molecular and cellular levels. In this review, we describe our current understanding of Wallerian degeneration, focusing on the molecular players and mechanisms that mediate the injury response, activate the degenerative program, transduce the death signal, execute the destruction order, and finally, clear away the debris. By highlighting the starring roles and sketching out the molecular script of Wallerian degeneration, we hope to provide a useful framework to understand Wallerian and Wallerian-like degeneration and to lay a foundation for developing new therapeutic strategies to treat axon degeneration in neural injury as well as in neurodegenerative disease.