Augustus Waller’s foresight realized: SARM1 in peripheral neuropathies

• Published in: Current opinion in neurobiology 2024-08, Vol.87, p.102884, Article 102884
• Main Author: Geisler, Stefanie
• Format: Article
• Language: English
• Subjects: Animals; Armadillo Domain Proteins - genetics; Armadillo Domain Proteins - metabolism; Axons - metabolism; Axons - pathology; Axons - physiology; Cytoskeletal Proteins - genetics; Cytoskeletal Proteins - metabolism; Humans; Peripheral Nervous System Diseases - genetics; Peripheral Nervous System Diseases - pathology
• ISSN: 0959-4388; 1873-6882; 1873-6882
• DOI: 10.1016/j.conb.2024.102884

Peripheral neuropathy is a common neurodegenerative condition characterized by numbness, tingling, pain, and weakness that frequently starts in the distal limbs. Arising from multiple etiologies, many peripheral neuropathies exhibit a slowly progressive course due to axon degeneration for which no effective treatments exist. During the past decade, numerous crucial insights into mechanisms of axon degeneration in peripheral neuropathies emerged from experiments involving nerve-cutting procedures, revealing the central role of the SARM1 axon degeneration pathway in both. Here I review commonalities and differences in the role of SARM1 after nerve cut and in several acquired and inherited peripheral neuropathies. This new knowledge now paves the way for the development of therapeutics that directly address root causes of various kinds of neuropathies. •Axon degeneration in several acquired and hereditary neuropathies is mediated by SARM1.•Different upstream mechanisms lead to SARM1 activation.•Targeting SARM1 pathway may lead to effective therapies for peripheral neuropathies.