Zhang Kai, Jiang Mingsheng, Fang Yanshan
Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201203, China; email:
University of Chinese Academy of Sciences, Beijing 100049, China.
Annu Rev Genet. 2021 Nov 23;55:93-113. doi: 10.1146/annurev-genet-071819-103917. Epub 2021 Aug 5.
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.
近年来,在确定沃勒变性(Wallerian degeneration)的遗传成分方面取得了重大进展。沃勒变性是一个导致受损轴突进行性破坏和清除的过程。现在人们已经认识到,沃勒变性是一个活跃且动态的细胞过程,在分子和细胞水平上受到良好调控。在这篇综述中,我们描述了目前对沃勒变性的理解,重点关注介导损伤反应、激活退化程序、转导死亡信号、执行破坏指令并最终清除碎片的分子参与者和机制。通过突出沃勒变性的主要角色并勾勒出其分子脚本,我们希望提供一个有用的框架来理解沃勒变性和类沃勒变性,并为开发新的治疗策略奠定基础,以治疗神经损伤以及神经退行性疾病中的轴突退化。