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Potent activation of SARM1 by NMN analogue VMN underlies vacor neurotoxicity

By Andrea Loreto, Carlo Angeletti, Jonathan Gilley, Peter Arthur-Farraj, Elisa Merlini, Adolfo Amici, Laura M. Desrochers, Qi Wang, Giuseppe Orsomando, Michael P. Coleman

Posted 19 Sep 2020
bioRxiv DOI: 10.1101/2020.09.18.304261

SARM1 is intensively studied for its role in promoting axon degeneration in injury and disease. We identify VMN, a metabolite of the neurotoxin vacor, as a potent SARM1 activator, an action likely to underlie vacor neurotoxicity in humans. This study provides novel tools to study SARM1 regulation, supports drug discovery, further links programmed axon death to human disease and identifies a new model where axons are permanently rescued. ### Competing Interest Statement This work is in part funded by a BBSRC/AstraZeneca Industrial Partnership Award and Q.W. and L.M.D. were employees of AstraZeneca for part of the project.

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