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Advances in genetic technologies have allowed for efficient modeling of NDDs in animals and brought hope for new disease\u2010modifying medications. The complexity of the mammalian brain and the costs and time needed to identify and develop therapeutic leads limits progress. Modeling NDDs in invertebrates, such as the fruit fly <jats:italic>Drosophila melanogaster<\/jats:italic> and the nematode <jats:italic>Caenorhabditis elegans<\/jats:italic>, offers orders of magnitude increases in speed of genetic analysis and manipulation, and can be pursued at substantially reduced cost, providing an important, platform complement and inform research with mammalian NDD models. In this review, we describe how our efforts to exploit <jats:italic>C. elegans<\/jats:italic> for the study of neural signaling and health led to the discovery of a paralytic phenotype (swimming\u2010induced paralysis) associated with altered dopamine signaling and, surprisingly, to the discovery of a novel gene and pathway whose dysfunction in glial cells triggers neurodegeneration. Research to date on <jats:italic>swip\u201010<\/jats:italic> and its putative mammalian ortholog <jats:italic>MBLAC1<\/jats:italic>, suggests that a tandem analysis will offer insights into NDD mechanisms and insights into novel, disease\u2010modifying therapeutics.<\/jats:p>","DOI":"10.1002\/jcp.31125","type":"journal-article","created":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T19:46:39Z","timestamp":1696535199000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Sink or swim: Does a worm paralysis phenotype hold clues to neurodegenerative disease?"],"prefix":"10.1002","volume":"239","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4331-8516","authenticated-orcid":false,"given":"Peter","family":"Rodriguez","sequence":"first","affiliation":[{"name":"Department of Biomedical Science Charles E. Schmidt College of Medicine Boca Raton Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2182-6966","authenticated-orcid":false,"given":"Randy D.","family":"Blakely","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science Charles E. 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