Downregulation of glial genes involved in synaptic function mitigates Huntington's disease pathogenesis

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dc.citation.articleNumbere64564en_US
dc.citation.journalTitleeLifeen_US
dc.citation.volumeNumber10en_US
dc.contributor.authorOnur, Tarik Serefen_US
dc.contributor.authorLaitman, Andrewen_US
dc.contributor.authorZhao, Heen_US
dc.contributor.authorKeyho, Ryanen_US
dc.contributor.authorKim, Hyeminen_US
dc.contributor.authorWang, Jenniferen_US
dc.contributor.authorMair, Meganen_US
dc.contributor.authorWang, Huilanen_US
dc.contributor.authorLi, Lifangen_US
dc.contributor.authorPerez, Almaen_US
dc.contributor.authorde Haro, Mariaen_US
dc.contributor.authorWan, Ying-Wooien_US
dc.contributor.authorAllen, Geneveraen_US
dc.contributor.authorLu, Boxunen_US
dc.contributor.authorAl-Ramahi, Ismaelen_US
dc.contributor.authorLiu, Zhandongen_US
dc.contributor.authorBotas, Juanen_US
dc.date.accessioned2021-06-17T19:01:29Zen_US
dc.date.available2021-06-17T19:01:29Zen_US
dc.date.issued2021en_US
dc.description.abstractMost research on neurodegenerative diseases has focused on neurons, yet glia help form and maintain the synapses whose loss is so prominent in these conditions. To investigate the contributions of glia to Huntington's disease (HD), we profiled the gene expression alterations of Drosophila expressing human mutant Huntingtin (mHTT) 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 dNRXN3 function in glia was sufficient to improve the phenotype of flies expressing mHTT 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.en_US
dc.identifier.citationOnur, Tarik Seref, Laitman, Andrew, Zhao, He, et al.. "Downregulation of glial genes involved in synaptic function mitigates Huntington's disease pathogenesis." <i>eLife,</i> 10, (2021) eLife: https://doi.org/10.7554/eLife.64564.en_US
dc.identifier.digitalelife-64564-v2en_US
dc.identifier.doihttps://doi.org/10.7554/eLife.64564en_US
dc.identifier.urihttps://hdl.handle.net/1911/110741en_US
dc.language.isoengen_US
dc.publishereLifeen_US
dc.rightsThis article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleDownregulation of glial genes involved in synaptic function mitigates Huntington's disease pathogenesisen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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