{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T01:55:44Z","timestamp":1777686944975,"version":"3.51.4"},"reference-count":47,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T00:00:00Z","timestamp":1753228800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T00:00:00Z","timestamp":1753228800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100000887","name":"Huntington's Disease Society of America","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000887","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Huntington's Disease"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Human Huntington's disease (HD) is a genetic neurodegenerative disorder caused by the mutant\n                      <jats:italic toggle=\"yes\">HTT<\/jats:italic>\n                      gene containing CAG repeat expansions, resulting in motor dysfunction and behavioral deficits. CAG repeats of 40\u201353 occur in adult HD and 60\u2013120 repeats occur in early onset juvenile HD, differing from the normal range of 5\u201335 repeats.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      The\n                      <jats:italic toggle=\"yes\">HTT<\/jats:italic>\n                      gene is translated to the huntingtin (HTT) protein that interacts with proteins in the development of HD. There have been few studies of HTT protein interactors in human HD brain. Therefore, this study evaluated the hypothesis that dysregulation of HTT protein interactors occurs in human juvenile HD brains.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The strategy of this study was to analyze proteomic data of human juvenile HD brain putamen and cortex regions for dysregulation of HTT interacting proteins, using a database that we compiled of HTT interactors identified in HD model systems from yeast to HD mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Results showed significant dysregulation of HTT protein interactors of mitochondria, signal transduction, RNA splicing, chromatin organization, translation, membrane trafficking, endocytosis, vesicle, protein modification, granule membrane, and macroautophagy pathways. The majority of downregulated and upregulated HTT interactors occurred in the putamen region compared to cortex. Dysregulation displayed downregulation of mitochondria and signal transduction interactors, combined with upregulation of RNA splicing, chromatin organization, and translational interactors. Network analysis revealed interactions among clusters of HTT interactors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings demonstrate prevalent dysregulation of HTT protein interactors in human juvenile HD brain, especially in the putamen region that controls movement deficits in HD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/18796397251358348","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T06:59:22Z","timestamp":1753340362000},"page":"354-368","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Dysregulation of huntingtin interacting protein networks in human juvenile Huntington's disease brain"],"prefix":"10.1177","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1541-0240","authenticated-orcid":false,"given":"Sonia","family":"Podvin","sequence":"first","affiliation":[{"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6548-9658","authenticated-orcid":false,"given":"Brin","family":"Rosenthal","sequence":"additional","affiliation":[{"name":"Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, CA, USA"},{"name":"Center for Computational Biology &amp; Bioinformatics, University of California, San Diego, La Jolla, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles","family":"Mosier","sequence":"additional","affiliation":[{"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9685-233X","authenticated-orcid":false,"given":"Enlin","family":"Wei","sequence":"additional","affiliation":[{"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0117-7444","authenticated-orcid":false,"given":"Kathleen M","family":"Fisch","sequence":"additional","affiliation":[{"name":"Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, CA, USA"},{"name":"Center for Computational Biology &amp; Bioinformatics, University of California, San Diego, La Jolla, CA, USA"},{"name":"Department of Obstetrics, Gynecology &amp; Reproductive Sciences, University of California, San Diego, La Jolla, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6461-7024","authenticated-orcid":false,"given":"Vivian","family":"Hook","sequence":"additional","affiliation":[{"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA"},{"name":"Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, CA, USA"},{"name":"Department of Neuroscience and Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2025,7,23]]},"reference":[{"key":"e_1_3_4_2_2","first-page":"971","article-title":"A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes","volume":"72","author":"The Huntington's Disease Collaborative Research Group","year":"1999","unstructured":"The Huntington's Disease Collaborative Research Group. 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