University of Massachusetts Medical School Faculty Publications

Title

Emergence of SARM1 as a Potential Therapeutic Target for Wallerian-type Diseases

UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology; Program in Chemical Biology; Thompson Lab; Graduate School of Biomedical Sciences

Publication Date

2020-01-16

Document Type

Article

Disciplines

Amino Acids, Peptides, and Proteins | Biochemistry | Enzymes and Coenzymes | Medicinal-Pharmaceutical Chemistry | Molecular and Cellular Neuroscience | Molecular Biology | Nervous System Diseases | Therapeutics

Abstract

Wallerian degeneration is a neuronal death pathway that is triggered in response to injury or disease. Death was thought to occur passively until the discovery of a mouse strain, i.e., Wallerian degeneration slow (WLD(S)), which was resistant to degeneration. Given that the WLD(S) mouse encodes a gain-of-function fusion protein, its relevance to human disease was limited. The later discovery that SARM1 (sterile alpha and toll/interleukin receptor [TIR] motif-containing protein 1) promotes Wallerian degeneration suggested the existence of a pathway that might be targeted therapeutically. More recently, SARM1 was found to execute degeneration by hydrolyzing NAD(+). Notably, SARM1 knockdown or knockout prevents neuron degeneration in response to a range of insults that lead to peripheral neuropathy, traumatic brain injury, and neurodegenerative disease. Here, we discuss the role of SARM1 in Wallerian degeneration and the opportunities to target this enzyme therapeutically.

Keywords

NAD(+), SARM1, neurodegeneration, therapeutics

DOI of Published Version

10.1016/j.chembiol.2019.11.002

Source

Loring HS, Thompson PR. Emergence of SARM1 as a Potential Therapeutic Target for Wallerian-type Diseases. Cell Chem Biol. 2020 Jan 16;27(1):1-13. doi: 10.1016/j.chembiol.2019.11.002. Epub 2019 Nov 21. PMID: 31761689; PMCID: PMC6980728. Link to article on publisher's site

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

Cell chemical biology

PubMed ID

31761689

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