Loss of Sarm1 does not suppress motor neuron degeneration in the SOD1G93A mouse model of amyotrophic lateral sclerosis

Peters, Owen ORCID: https://orcid.org/0000-0002-6824-0663, Lewis, Elizabeth A, Osterloh, Jeannette M, Weiss, Alexandra, Salameh, Johnny S, Metterville, Jake, Brown, Robert H and Freeman, Marc R 2018. Loss of Sarm1 does not suppress motor neuron degeneration in the SOD1G93A mouse model of amyotrophic lateral sclerosis. Human Molecular Genetics 27 (21) , pp. 3761-3771. 10.1093/hmg/ddy260

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Abstract

Axon degeneration occurs in all neurodegenerative diseases, but the molecular pathways regulating axon destruction during neurodegeneration are poorly understood. Sterile Alpha and TIR Motif Containing 1 (Sarm1) is an essential component of the prodegenerative pathway driving axon degeneration after axotomy and represents an appealing target for therapeutic intervention in neurological conditions involving axon loss. Amyotrophic lateral sclerosis (ALS) is characterized by rapid, progressive motor neuron degeneration and muscle atrophy, causing paralysis and death. Patient tissue and animal models of ALS show destruction of upper and lower motor neuron cell bodies and loss of their associated axons. Here, we investigate whether loss of Sarm1 can mitigate motor neuron degeneration in the SOD1G93A mouse model of ALS. We found no change in survival, behavioral, electrophysiogical or histopathological outcomes in SOD1G93A mice null for Sarm1. Blocking Sarm1-mediated axon destruction alone is therefore not sufficient to suppress SOD1G93A-induced neurodegeneration. Our data suggest the molecular pathways driving axon loss in ALS may be Sarm1-independent or involve genetic pathways that act in a redundant fashion with Sarm1.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Publisher:	Oxford University Press
ISSN:	0964-6906
Date of First Compliant Deposit:	29 August 2018
Date of Acceptance:	9 July 2018
Last Modified:	04 May 2023 23:44
URI:	https://orca.cardiff.ac.uk/id/eprint/114455

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