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
PubMed ID
30010873
Repository Citation
Peters, Owen M.; Lewis, Elizabeth A.; Osterloh, Jeannette M.; Weiss, Alexandra; Salameh, Johnny; Metterville, Jake P.; Brown, Robert H. Jr.; and Freeman, Marc R., "Loss of Sarm1 does not suppress motor neuron degeneration in the SOD1G93A mouse model of amyotrophic lateral sclerosis" (2018). Neurobiology Publications and Presentations. 234.
https://escholarship.umassmed.edu/neurobiology_pp/234
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Included in
Developmental Neuroscience Commons, Molecular and Cellular Neuroscience Commons, Molecular Genetics Commons, Nervous System Diseases Commons