{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T19:06:46Z","timestamp":1790795206321,"version":"4.1.0"},"reference-count":39,"publisher":"The Company of Biologists","issue":"12","license":[{"start":{"date-parts":[[2021,2,11]],"date-time":"2021-02-11T00:00:00Z","timestamp":1613001600000},"content-version":"vor","delay-in-days":72,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100007249","name":"University of Minnesota","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007249","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000156","name":"Fonds de Recherche du Qu\u00e9bec - Sant\u00e9","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000156","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021356","name":"La Fondation du Grand d\u00e9fi Pierre Lavoie","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100021356","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,12,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Spinal muscular atrophy (SMA) is a devastating autosomal recessive neuromuscular disease resulting in muscle atrophy and neurodegeneration, and is the leading genetic cause of infant death. SMA arises when there are homozygous deletion mutations in the human SMN1 gene, leading to a decrease in corresponding SMN1 protein. Although SMN1 is expressed across multiple tissue types, much of the previous research into SMA focused on the neuronal aspect of the disease, overlooking many of the potential non-neuronal aspects of the disease. Therefore, we sought to address this gap in knowledge by modeling SMA in the nematode Caenorhabditis elegans. We mutated a previously uncharacterized allele, which resulted in the onset of mild SMA-like phenotypes, allowing us to monitor the onset of phenotypes at different stages. We observed that these mutant animals recapitulated many key features of the human disease, and most importantly, we observed that muscle dysfunction preceded neurodegeneration. Furthermore, we tested the therapeutic efficacy of targeting endoplasmic reticulum (ER) stress in non-neuronal cells and found it to be more effective than targeting ER stress in neuronal cells. We also found that the most potent therapeutic potential came from a combination of ER- and neuromuscular junction-targeted drugs. Together, our results suggest an important non-neuronal component of SMA pathology and highlight new considerations for therapeutic intervention.<\/jats:p>","DOI":"10.1242\/dmm.041350","type":"journal-article","created":{"date-parts":[[2020,10,8]],"date-time":"2020-10-08T17:05:29Z","timestamp":1602176729000},"source":"Crossref","is-referenced-by-count":9,"title":["Modulating the endoplasmic reticulum stress response attenuates neurodegeneration in a\n                    <i>Caenorhabditis<\/i>\n                    \u2008\n                    <i>elegans<\/i>\n                    model of spinal muscular atrophy"],"prefix":"10.1242","volume":"13","author":[{"given":"James J.","family":"Doyle","sequence":"first","affiliation":[{"name":"McGill University 1 Division of Experimental Medicine , , Montreal, Quebec H4A 3J1 , Canada"},{"name":"Metabolic Disorders and Complications, Research Institute of the McGill University Health Centre 2 , Montreal, Quebec H4A 3J1 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celine","family":"Vrancx","sequence":"additional","affiliation":[{"name":"University of Montreal 3 Centre de Recherche du Centre Hospitalier de l'Universit\u00e9 de Montr\u00e9al and Department of Neuroscience , , Montreal, Quebec H2X 0A9 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Maios","sequence":"additional","affiliation":[{"name":"University of Montreal 3 Centre de Recherche du Centre Hospitalier de l'Universit\u00e9 de Montr\u00e9al and Department of Neuroscience , , Montreal, Quebec H2X 0A9 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey","family":"Labarre","sequence":"additional","affiliation":[{"name":"University of Montreal 3 Centre de Recherche du Centre Hospitalier de l'Universit\u00e9 de Montr\u00e9al and Department of Neuroscience , , Montreal, Quebec H2X 0A9 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunmoogum A.","family":"Patten","sequence":"additional","affiliation":[{"name":"INRS-Institut Armand-Frappier 4 , Laval, Quebec H7V 1B7 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3333-2445","authenticated-orcid":false,"given":"J. Alex","family":"Parker","sequence":"additional","affiliation":[{"name":"University of Montreal 3 Centre de Recherche du Centre Hospitalier de l'Universit\u00e9 de Montr\u00e9al and Department of Neuroscience , , Montreal, Quebec H2X 0A9 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2020,12,22]]},"reference":[{"key":"2024061302334429500_DMM041350C1","doi-asserted-by":"publisher","first-page":"13932","DOI":"10.1523\/JNEUROSCI.1515-10.2010","article-title":"A dominant mutation in a neuronal acetylcholine receptor subunit leads to motor neuron degeneration in Caenorhabditis elegans","volume":"30","author":"Barbagallo","year":"2010","journal-title":"J. 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