{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T01:59:11Z","timestamp":1777687151564,"version":"3.51.4"},"reference-count":49,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2016,9,24]],"date-time":"2016-09-24T00:00:00Z","timestamp":1474675200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Huntington's Disease"],"published-print":{"date-parts":[[2016,9,24]]},"abstract":"<jats:p>Background: Mutant huntingtin (mHTT) is encoded by the Huntington\u2019s disease (HD) gene and its accumulation in the brain contributes to HD pathogenesis. Reducing mHTT levels through activation of the autophagosome-lysosomal pathway may have therapeutic benefit. Transcription factor EB (TFEB) regulates lysosome biogenesis and autophagy.<\/jats:p>\n                  <jats:p>Objective: To examine if increasing TFEB protein levels in HD mouse striatum induces autophagy and influences mHTT levels.<\/jats:p>\n                  <jats:p>\n                    Methods: We introduced cDNA encoding TFEB with an HA tag (TFEB-HA) under the control of neuron specific synapsin 1 promoter into the striatum of 3 month old HD\n                    <jats:sup>Q175\/Q7<\/jats:sup>\n                    mice using adeno-associated virus AAV2\/9. The levels of exogenous TFEB were analyzed using qPCR and Western blot. Proteins involved in autophagy, levels of huntingtin, and striatal-enriched proteins were examined using biochemical and\/or immunohistochemical methods.\n                  <\/jats:p>\n                  <jats:p>\n                    Results: In HD mice expressing TFEB-HA, HA immunoreactivity distributed throughout the striatum in neuronal cell bodies and processes and preferentially in neuronal nuclei and overlapped with a loss of DARPP32 immunoreactivity. TFEB-HA mRNA and protein were detected in striatal lysates. There were increased levels of proteins involved with autophagosome\/lysosome activity including LAMP-2A, LC3II, and cathepsin D and reduced levels of mutant HTT and the striatal enriched proteins DARPP32 and PDE10A. Compared to WT mice, HD\n                    <jats:sup>Q175\/Q7<\/jats:sup>\n                    mice had elevated levels of the ER stress protein GRP78\/BiP and with TFEB-HA expression, increased levels of the astrocyte marker GFAP and pro-caspase 3.\n                  <\/jats:p>\n                  <jats:p>\n                    Conclusion: These results suggest that TFEB expression in the striatum of HD\n                    <jats:sup>Q175\/Q7<\/jats:sup>\n                    mice stimulates autophagy and lysosome activity, and lowers mHTT, but may also increase a neuronal stress response.\n                  <\/jats:p>","DOI":"10.3233\/jhd-160211","type":"journal-article","created":{"date-parts":[[2016,9,27]],"date-time":"2016-09-27T12:11:03Z","timestamp":1474978263000},"page":"249-260","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":39,"title":["Autophagy Activation by Transcription Factor EB (TFEB) in Striatum of HD\n                    <sup>Q175\/Q7<\/sup>\n                    Mice"],"prefix":"10.1177","volume":"5","author":[{"given":"Petr","family":"Vodicka","sequence":"first","affiliation":[{"name":"Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathryn","family":"Chase","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Cell Biology, University of Massachusetts, Worcester, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Iuliano","sequence":"additional","affiliation":[{"name":"Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adelaide","family":"Tousley","sequence":"additional","affiliation":[{"name":"Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dana T.","family":"Valentine","sequence":"additional","affiliation":[{"name":"Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ellen","family":"Sapp","sequence":"additional","affiliation":[{"name":"Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kimberly B.","family":"Kegel-Gleason","sequence":"additional","affiliation":[{"name":"Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel","family":"Sena-Esteves","sequence":"additional","affiliation":[{"name":"Department of Neurology, Horae Gene Therapy Center, University of Massachusetts Medical School, Albert Sherman Center, Worcester, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neil","family":"Aronin","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Cell Biology, University of Massachusetts, Worcester, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marian","family":"DiFiglia","sequence":"additional","affiliation":[{"name":"Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2016,9,24]]},"reference":[{"key":"ref001","doi-asserted-by":"publisher","DOI":"10.1023\/B:MCBI.0000041848.57020.57"},{"key":"ref002","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.01620"},{"key":"ref003","doi-asserted-by":"publisher","DOI":"10.4161\/auto.5338"},{"key":"ref004","doi-asserted-by":"publisher","DOI":"10.4161\/auto.4377"},{"key":"ref005","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1599207"},{"key":"ref006","doi-asserted-by":"publisher","DOI":"10.1038\/nature05291"},{"key":"ref007","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410420411"},{"key":"ref008","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-19-07268.2000"},{"key":"ref009","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2005.11.012"},{"key":"ref010","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0046834"},{"key":"ref011","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.025726"},{"key":"ref012","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg346"},{"key":"ref013","doi-asserted-by":"publisher","DOI":"10.1002\/path.2697"},{"key":"ref014","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M303800200"},{"key":"ref015","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq285"},{"key":"ref016","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.01114"},{"key":"ref017","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2012.11.018"},{"key":"ref018","doi-asserted-by":"publisher","DOI":"10.1007\/s109-1998-8099-y"},{"key":"ref019","doi-asserted-by":"publisher","DOI":"10.1126\/science.1101738"},{"key":"ref020","doi-asserted-by":"publisher","DOI":"10.1126\/science.273.5274.501"},{"key":"ref021","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.9.5606"},{"key":"ref022","doi-asserted-by":"publisher","DOI":"10.1126\/science.1174447"},{"key":"ref023","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201303671"},{"key":"ref024","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3788-13.2014"},{"key":"ref025","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0120819"},{"key":"ref026","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3003799"},{"key":"ref027","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(98)00724-0"},{"key":"ref028","doi-asserted-by":"publisher","DOI":"10.1369\/jhc.6A6930.2006"},{"key":"ref029","doi-asserted-by":"publisher","DOI":"10.1126\/science.1204592"},{"key":"ref030","doi-asserted-by":"publisher","DOI":"10.3233\/JHD-160195"},{"key":"ref031","doi-asserted-by":"publisher","DOI":"10.3233\/JHD-130081"},{"key":"ref032","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.321661"},{"key":"ref033","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2328-10.2010"},{"key":"ref034","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(95)90346-1"},{"key":"ref035","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.9.1107"},{"key":"ref036","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1305623110"},{"key":"ref037","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3114"},{"key":"ref038","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0505801102"},{"key":"ref039","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn157"},{"key":"ref040","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2014.05.044"},{"key":"ref041","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2009.08.002"},{"issue":"5","key":"ref042","first-page":"694","volume":"17","author":"Tong X","year":"2014","journal-title":"1 ion channel deficits contribute to neuronal dysfunction in Huntington\u2019s disease model mice. Nat Neurosci"},{"key":"ref043","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-199805000-00001"},{"key":"ref044","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2518-08.2008"},{"key":"ref045","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2014.01.001"},{"key":"ref046","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0013417"},{"key":"ref047","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2006.01.012"},{"key":"ref048","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2007.12.025"},{"key":"ref049","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2012.03.074"}],"container-title":["Journal of Huntington's Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JHD-160211","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.3233\/JHD-160211","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JHD-160211","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T08:57:12Z","timestamp":1777453032000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.3233\/JHD-160211"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,9,24]]},"references-count":49,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2016,9,24]]}},"alternative-id":["10.3233\/JHD-160211"],"URL":"https:\/\/doi.org\/10.3233\/jhd-160211","relation":{},"ISSN":["1879-6397","1879-6400"],"issn-type":[{"value":"1879-6397","type":"print"},{"value":"1879-6400","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,9,24]]}}}