轴突自我毁灭：SARM1、丝裂原活化蛋白激酶和烟酰胺腺嘌呤二核苷酸代谢之间的新联系

Gerdts Josiah, Summers Daniel W, Milbrandt Jeffrey, DiAntonio Aaron

Department of Genetics, Washington University School of Medicine in St. Louis, 660 Euclid Avenue, St. Louis, MO 63110, USA.

Department of Genetics, Washington University School of Medicine in St. Louis, 660 Euclid Avenue, St. Louis, MO 63110, USA; Department of Developmental Biology, Washington University School of Medicine in St. Louis, 660 Euclid Avenue, St. Louis, MO 63110, USA.

Neuron. 2016 Feb 3;89(3):449-60. doi: 10.1016/j.neuron.2015.12.023.

Wallerian axon degeneration is a form of programmed subcellular death that promotes axon breakdown in disease and injury. Active degeneration requires SARM1 and MAP kinases, including DLK, while the NAD+ synthetic enzyme NMNAT2 prevents degeneration. New studies reveal that these pathways cooperate in a locally mediated axon destruction program, with NAD+ metabolism playing a central role. Here, we review the biology of Wallerian-type axon degeneration and discuss the most recent findings, with special emphasis on critical signaling events and their potential as therapeutic targets for axonopathy.

华勒氏轴突退变是一种程序性亚细胞死亡形式，在疾病和损伤中促进轴突分解。主动退变需要SARM1和丝裂原活化蛋白激酶（包括DLK），而NAD⁺合成酶NMNAT2可防止退变。新研究表明，这些途径在局部介导的轴突破坏程序中协同作用，其中NAD⁺代谢起着核心作用。在这里，我们综述华勒氏型轴突退变的生物学，并讨论最新发现，特别强调关键信号事件及其作为轴突病治疗靶点的潜力。