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

Simple item page
dc.citation.articleNumbere64564
dc.citation.journalTitleeLife
dc.citation.volumeNumber10
dc.contributor.authorOnur, Tarik Seref
dc.contributor.authorLaitman, Andrew
dc.contributor.authorZhao, He
dc.contributor.authorKeyho, Ryan
dc.contributor.authorKim, Hyemin
dc.contributor.authorWang, Jennifer
dc.contributor.authorMair, Megan
dc.contributor.authorWang, Huilan
dc.contributor.authorLi, Lifang
dc.contributor.authorPerez, Alma
dc.contributor.authorde Haro, Maria
dc.contributor.authorWan, Ying-Wooi
dc.contributor.authorAllen, Genevera
dc.contributor.authorLu, Boxun
dc.contributor.authorAl-Ramahi, Ismael
dc.contributor.authorLiu, Zhandong
dc.contributor.authorBotas, Juan
dc.date.accessioned2021-06-17T19:01:29Z
dc.date.available2021-06-17T19:01:29Z
dc.date.issued2021
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.
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.
dc.identifier.digitalelife-64564-v2
dc.identifier.doihttps://doi.org/10.7554/eLife.64564
dc.identifier.urihttps://hdl.handle.net/1911/110741
dc.language.isoeng
dc.publishereLife
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.
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleDownregulation of glial genes involved in synaptic function mitigates Huntington's disease pathogenesis
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
elife-64564-v2.pdf
Size:
3.59 MB
Format:
Adobe Portable Document Format
Download
Collections
Faculty Publications
Computer Science Publications
ECE Publications
Statistics Publications