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

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    Authors
    Loring, Heather S.
    Thompson, Paul R
    UMass Chan Affiliations
    Graduate School of Biomedical Sciences
    Thompson Lab
    Program in Chemical Biology
    Department of Biochemistry and Molecular Pharmacology
    Document Type
    Journal Article
    Publication Date
    2020-01-16
    Keywords
    NAD(+)
    SARM1
    neurodegeneration
    therapeutics
    Amino Acids, Peptides, and Proteins
    Biochemistry
    Enzymes and Coenzymes
    Medicinal-Pharmaceutical Chemistry
    Molecular and Cellular Neuroscience
    Molecular Biology
    Nervous System Diseases
    Therapeutics
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    Link to Full Text
    https://doi.org/10.1016/j.chembiol.2019.11.002
    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.
    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

    DOI
    10.1016/j.chembiol.2019.11.002
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/29439
    PubMed ID
    31761689
    Related Resources

    Link to Article in PubMed

    ae974a485f413a2113503eed53cd6c53
    10.1016/j.chembiol.2019.11.002
    Scopus Count
    Collections
    Morningside Graduate School of Biomedical Sciences Scholarly Publications
    UMass Chan Faculty and Researcher Publications
    Thompson Lab Publications

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