title: miR-196a Ameliorates Cytotoxicity and Cellular Phenotype in Transgenic Huntington's Disease Monkey Neural Cells.
abstract: Huntington's disease (HD) is an inherited neurodegenerative disorder caused by the expansion of polyglutamine (polyQ) tract that leads to motor, cognitive and psychiatric impairment. Currently there is no cure for HD. A transgenic HD nonhuman primate (HD-NHP) model was developed with progressive development of clinical and pathological features similar to human HD, which suggested the potential preclinical application of the HD-NHP model. Elevated expression of miR-196a was observed in both HD-NHP and human HD brains. Cytotoxicity and apoptosis were ameliorated by the overexpression of miR-196a in HD-NHP neural progenitor cells (HD-NPCs) and differentiated neural cells (HD-NCs). The expression of apoptosis related gene was also down regulated. Mitochondrial morphology and activity were improved as indicated by mitotracker staining and the upregulation of CBP and PGC-1α in HD-NPCs overexpressing miR-196a. Here we demonstrated the amelioration of HD cellular phenotypes in HD-NPCs and HD-NCs overexpressing miR-196a. Our results also suggested the regulatory role of miR-196a in HD pathogenesis that may hold the key for understanding molecular regulation in HD and developing novel therapeutics.
authors.affiliation: Yerkes National Primate Research Center, 954 Gatewood Rd. N.E., Atlanta, GA, 39329, United States of America.|Department of Human Genetics, Emory University School of Medicine, 615 Michael St., Atlanta, GA 30322, United States of America.|Embryo Technology and Stem Cell Research Center, School of Biotechnology, Suranaree University of Technology, Nakhon Ratchasima 30000, Thailand.
authors.forename: Tanut
authors.identifier: http://orcid.org/0000-0002-3716-8179
authors.initials: T
authors.lastname: Kunkanjanawan
authors.affiliation: Yerkes National Primate Research Center, 954 Gatewood Rd. N.E., Atlanta, GA, 39329, United States of America.|Department of Human Genetics, Emory University School of Medicine, 615 Michael St., Atlanta, GA 30322, United States of America.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Carter
authors.affiliation: Yerkes National Primate Research Center, 954 Gatewood Rd. N.E., Atlanta, GA, 39329, United States of America.|Department of Human Genetics, Emory University School of Medicine, 615 Michael St., Atlanta, GA 30322, United States of America.
authors.forename: Melinda S
authors.initials: MS
authors.lastname: Prucha
authors.affiliation: Yerkes National Primate Research Center, 954 Gatewood Rd. N.E., Atlanta, GA, 39329, United States of America.|Department of Human Genetics, Emory University School of Medicine, 615 Michael St., Atlanta, GA 30322, United States of America.
authors.forename: Jinjing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Embryo Technology and Stem Cell Research Center, School of Biotechnology, Suranaree University of Technology, Nakhon Ratchasima 30000, Thailand.
authors.forename: Rangsun
authors.initials: R
authors.lastname: Parnpai
authors.affiliation: Yerkes National Primate Research Center, 954 Gatewood Rd. N.E., Atlanta, GA, 39329, United States of America.|Department of Human Genetics, Emory University School of Medicine, 615 Michael St., Atlanta, GA 30322, United States of America.
authors.forename: Anthony W S
authors.initials: AW
authors.lastname: Chan
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D004195:Disease Models, Animal; D006801:Humans; D006816:Huntington Disease / Q000473:pathology*; D035683:MicroRNAs / Q000502:physiology*; D008928:Mitochondria / Q000378:metabolism; D058953:Neural Stem Cells / Q000378:metabolism*; D010641:Phenotype
chemical_list: C542543:MIRN196 microRNA, human; D035683:MicroRNAs