《生命科学》 2017, 29(3): 245-250
摘 要：摘 要：沃勒氏退行性病变是许多神经退行性疾病的重要病理过程之一。不同损伤条件引发的神经元轴突结构瓦解是沃勒氏退行性病变的典型特征。对于沃勒氏退行性病变缓慢型(Wallerian degeneration slow， WldS) 突变小鼠及其相关WldS 突变蛋白的研究提示，沃勒氏退行性病变受到轴突内特有信号通路的调控。领域内的研究工作一直致力于阐明沃勒氏退行性病变的分子机制，并在过去几年中揭示了Sarm1-MAPK 信号通路在沃勒氏退行性病变中的核心作用。Sarm1-MAPK 信号通路在轴突损伤后改变能量代谢平衡，导致钙激活中性蛋白酶的活化，最终引起受损轴突结构的物理性瓦解。深入研究沃勒氏退行性病变分子机制对预防和治疗神经退行性疾病有着至关重要的意义。
Abstract: Abstract: Wallerian degeneration has been recognized as a key pathological feature in many neurodegenerative disorders. In particular， the process of Wallerian degeneration eliminates damaged axons following different insults. The discovery of the Wallerian degeneration slow (WldS) mutant mice and the subsequent characterization of WldS have suggested that Wallerian degeneration might be regulated by certain signaling mechanpism intrinsic to axons. Over the past few years， studies have revealed that Sarm1-MAPK pathway represents the central mechanism of initiating Wallerian degeneration. The Sarm1-MAPK pathway exerts its pro-degenerative function by destructing axonal energy homeostasis， which activates the Ca2+-dependent proteases calpains， leading to the breakdown of damaged axons. The in-depth knowledge of the molecular pathways regulating Wallerian degeneration will provide key insights to our understanding of neurodegeneration， and at the same time， help reveal novel therapeutic targets for battling those debilitating disorders.
