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Currently, no cure is available. It is becoming increasingly apparent that mutant Huntingtin (<jats:styled-content style=\"fixed-case\">HTT<\/jats:styled-content>) impairs metabolic homeostasis and causes transcriptional dysregulation. The peroxisome proliferator\u2010activated receptor gamma (<jats:styled-content style=\"fixed-case\">PPAR<\/jats:styled-content>\u2010\u03b3) is a transcriptional factor that plays a key role in regulating genes involved in energy metabolism; recent studies demonstrated that <jats:styled-content style=\"fixed-case\">PPAR<\/jats:styled-content>\u2010\u03b3 activation prevented mitochondrial depolarization in cells expressing mutant <jats:styled-content style=\"fixed-case\">HTT<\/jats:styled-content> and attenuated neurodegeneration in various models of neurodegenerative diseases. <jats:styled-content style=\"fixed-case\">PPAR<\/jats:styled-content>\u2010\u03b3\u2010coactivator 1\u03b1 (<jats:styled-content style=\"fixed-case\">PGC<\/jats:styled-content>\u20101 \u03b1) transcription activity is also impaired by mutant <jats:styled-content style=\"fixed-case\">HTT<\/jats:styled-content>. We now report that the <jats:styled-content style=\"fixed-case\">PPAR<\/jats:styled-content>\u2010\u03b3 agonist, rosiglitazone (<jats:styled-content style=\"fixed-case\">RSG<\/jats:styled-content>), significantly attenuated mutant <jats:styled-content style=\"fixed-case\">HTT<\/jats:styled-content>\u2010induced toxicity in striatal cells and that the protective effect of <jats:styled-content style=\"fixed-case\">RSG<\/jats:styled-content> is mediated by activation of <jats:styled-content style=\"fixed-case\">PPAR<\/jats:styled-content>\u2010\u03b3. Moreover, chronic administration of <jats:styled-content style=\"fixed-case\">RSG<\/jats:styled-content> (10\u00a0mg\/kg\/day, i.p) significantly improved motor function and attenuated hyperglycemia in N171\u201082Q <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content> mice. <jats:styled-content style=\"fixed-case\">RSG<\/jats:styled-content> administration rescued <jats:styled-content style=\"fixed-case\">brain derived neurotrophic factor(BDNF)<\/jats:styled-content> deficiency in the cerebral cortex, and prevented loss of orexin\u2010A\u2010immunopositive neurons in the hypothalamus of N171\u201082Q <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content> mice. <jats:styled-content style=\"fixed-case\">RSG<\/jats:styled-content> also prevented <jats:styled-content style=\"fixed-case\">PGC<\/jats:styled-content>\u20101\u03b1 reduction and increased Sirt6 protein levels in <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content> mouse brain. Our results suggest that modifying the <jats:styled-content style=\"fixed-case\">PPAR<\/jats:styled-content>\u2010\u03b3 pathway plays a beneficial role in rescuing motor function as well as glucose metabolic abnormalities in <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/jnc.12190","type":"journal-article","created":{"date-parts":[[2013,2,4]],"date-time":"2013-02-04T15:25:13Z","timestamp":1359991513000},"page":"410-419","source":"Crossref","is-referenced-by-count":116,"title":["Neuroprotective effects of <scp>PPAR<\/scp>\u2010\u03b3 agonist rosiglitazone in N171\u201082Q mouse model of Huntington's disease"],"prefix":"10.1111","volume":"125","author":[{"given":"Jing","family":"Jin","sequence":"first","affiliation":[{"name":"Division of Neurobiology Department of Psychiatry and Behavioral Sciences Johns Hopkins University School of Medicine Baltimore Maryland 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