UMMS Affiliation

Department of Neurobiology; Department of Neurology; Freeman Lab; Graduate School of Biomedical Sciences, Neuroscience Program

Publication Date

2018-07-14

Document Type

Article

Disciplines

Developmental Neuroscience | Molecular and Cellular Neuroscience | Molecular Genetics | Nervous System Diseases

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.

Keywords

amyotrophic lateral sclerosis, axon, axotomy, mice, transgenic, motor neurons, nerve degeneration, neurodegenerative disorders, sod1 gene, tissue degeneration

Rights and Permissions

©The Author(s) 2018. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

DOI of Published Version

10.1093/hmg/ddy260

Source

Hum Mol Genet. 2018 Jul 14. pii: 5053938. doi: 10.1093/hmg/ddy260. Link to article on publisher's site

Journal/Book/Conference Title

Human molecular genetics

Related Resources

Link to Article in PubMed

PubMed ID

30010873

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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