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To investigate the contributions of glia to Huntington's disease (HD), we profiled the gene expression alterations of\n                    <jats:italic>Drosophila<\/jats:italic>\n                    expressing human mutant\n                    <jats:italic>Huntingtin<\/jats:italic>\n                    (m\n                    <jats:italic>HTT<\/jats:italic>\n                    ) in either glia or neurons and compared these changes to what is observed in HD human and HD mice striata. A large portion of conserved genes are concordantly dysregulated across the three species; we tested these genes in a high-throughput behavioral assay and found that downregulation of genes involved in synapse assembly mitigated pathogenesis and behavioral deficits. To our surprise, reducing d\n                    <jats:italic>NRXN3<\/jats:italic>\n                    function in glia was sufficient to improve the phenotype of flies expressing m\n                    <jats:italic>HTT<\/jats:italic>\n                    in neurons, suggesting that mHTT's toxic effects in glia ramify throughout the brain. This supports a model in which dampening synaptic function is protective because it attenuates the excitotoxicity that characterizes HD.\n                  <\/jats:p>","DOI":"10.7554\/elife.64564","type":"journal-article","created":{"date-parts":[[2021,4,19]],"date-time":"2021-04-19T08:06:35Z","timestamp":1618819595000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.64564","source":"Crossref","is-referenced-by-count":41,"title":["Downregulation of glial genes involved in synaptic function mitigates Huntington's disease pathogenesis"],"prefix":"10.7554","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3234-6263","authenticated-orcid":true,"given":"Tarik Seref","family":"Onur","sequence":"first","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States"},{"name":"Jan and Dan Duncan Neurological Research Institute at Texas Children\u2019s Hospital, Houston, United States"},{"name":"Genetics & Genomics 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