{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T14:03:12Z","timestamp":1787752992341,"version":"build-2784847793"},"reference-count":75,"publisher":"National Academy of Sciences","issue":"38","license":[{"start":{"date-parts":[[2020,3,4]],"date-time":"2020-03-04T00:00:00Z","timestamp":1583280000000},"content-version":"vor","delay-in-days":182,"URL":"https:\/\/www.pnas.org\/site\/aboutpnas\/licenses.xhtml"}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2019,9,17]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    Huntington\u2019s disease (HD) is a dominantly inherited neurodegenerative disorder caused by expansion of CAG repeats in\n                    <jats:italic>huntingtin<\/jats:italic>\n                    (Htt). The mutant Htt protein containing expanded polyglutamine is prone to misfolding and aggregation; however, the cytotoxicity of mutant Htt aggregation remains elusive. Here, we describe the cytotoxicity of mutant Htt aggregates in distinct neuronal compartments, reveal the amyloid-like biochemical properties of aggregates that correlate with the severity of neurodegeneration, and demonstrate the robust neuroprotection of NMNAT, a conserved NAD\n                    <jats:sup>+<\/jats:sup>\n                    synthase, through reducing Htt aggregation and neutralizing the damaging adhesive property of aggregates. Importantly, induction of Nmnat postphenotypic onset neutralizes cytotoxicity and exerts immediate neuroprotection. Our study provides insights into the neuropathology of HD and implications of aggregate-neutralizing as a therapeutic strategy.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1904563116","type":"journal-article","created":{"date-parts":[[2019,9,17]],"date-time":"2019-09-17T17:45:26Z","timestamp":1568742326000},"page":"19165-19175","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":39,"title":["Nmnat restores neuronal integrity by neutralizing mutant Huntingtin aggregate-induced progressive toxicity"],"prefix":"10.1073","volume":"116","author":[{"given":"Yi","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL 33136"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2823-7360","authenticated-orcid":false,"given":"Chong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL 33136"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianzun","family":"Tao","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL 33136"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer M.","family":"Brazill","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL 33136"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joun","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL 33136"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoraida","family":"Diaz-Perez","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL 33136"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. 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