轴突
神经科学
生物
神经毒性
NAD+激酶
变性(医学)
神经退行性变
轴突变性
化学
医学
病理
疾病
生物化学
毒性
有机化学
酶
作者
Helen Y. McGuinness,Weixi Gu,Yun Shi,Boštjan Kobe,Thomas Ve
出处
期刊:The Neuroscientist
[SAGE]
日期:2023-03-31
卷期号:: 107385842311625-107385842311625
被引量:10
标识
DOI:10.1177/10738584231162508
摘要
Axons are an essential component of the nervous system, and axon degeneration is an early feature of many neurodegenerative disorders. The NAD+ metabolome plays an essential role in regulating axonal integrity. Axonal levels of NAD+ and its precursor NMN are controlled in large part by the NAD+ synthesizing survival factor NMNAT2 and the pro-neurodegenerative NADase SARM1, whose activation triggers axon destruction. SARM1 has emerged as a promising axon-specific target for therapeutic intervention, and its function, regulation, structure, and role in neurodegenerative diseases have been extensively characterized in recent years. In this review, we first introduce the key molecular players involved in the SARM1-dependent axon degeneration program. Next, we summarize recent major advances in our understanding of how SARM1 is kept inactive in healthy neurons and how it becomes activated in injured or diseased neurons, which has involved important insights from structural biology. Finally, we discuss the role of SARM1 in neurodegenerative disorders and environmental neurotoxicity and its potential as a therapeutic target.
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