miR-196a Ameliorates Cytotoxicity and Cellular Phenotype in Transgenic Huntington's Disease Monkey Neural Cells
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 progressiv...
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| creator | Kunkanjanawan, Tanut Carter, Richard L Prucha, Melinda S Yang, Jinjing Parnpai, Rangsun Chan, Anthony W S |
| description | 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. |
| doi_str_mv | 10.1371/journal.pone.0162788 |
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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0162788</identifier><identifier>PMID: 27631085</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Age ; Animals ; Animals, Genetically Modified ; Apoptosis ; Biology and Life Sciences ; Biomarkers ; Brain research ; Brain-derived neurotrophic factor ; Cells (biology) ; Cognitive ability ; Cytotoxicity ; Dehydrogenases ; Disease Models, Animal ; Gene expression ; Genes ; Genetic aspects ; Genetic engineering ; Genetics ; High definition television ; Humans ; Huntington Disease - pathology ; Huntington's disease ; Huntingtons disease ; Medical research ; Medicine ; Medicine and Health Sciences ; MicroRNAs - physiology ; Mitochondria ; Mitochondria - metabolism ; Nervous system diseases ; Neural stem cells ; Neural Stem Cells - metabolism ; Neurodegenerative diseases ; Neurosciences ; Oxidative stress ; Pathogenesis ; Phenotype ; Polyglutamine ; Primates ; Progenitor cells ; Research and Analysis Methods ; Rodents ; Stem cells ; Studies ; Toxicity ; Trinucleotide repeat diseases</subject><ispartof>PloS one, 2016-09, Vol.11 (9), p.e0162788-e0162788</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Kunkanjanawan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2016 Kunkanjanawan et al 2016 Kunkanjanawan et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c725t-b98ad49314c3ef560400de7183df26294754d94e02a0f2303e91087bdbe6c0fd3</citedby><cites>FETCH-LOGICAL-c725t-b98ad49314c3ef560400de7183df26294754d94e02a0f2303e91087bdbe6c0fd3</cites><orcidid>0000-0002-3716-8179</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5025087/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5025087/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,861,882,2096,2915,23847,27905,27906,53772,53774,79349,79350</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27631085$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Borchelt, David R</contributor><creatorcontrib>Kunkanjanawan, Tanut</creatorcontrib><creatorcontrib>Carter, Richard L</creatorcontrib><creatorcontrib>Prucha, Melinda S</creatorcontrib><creatorcontrib>Yang, Jinjing</creatorcontrib><creatorcontrib>Parnpai, Rangsun</creatorcontrib><creatorcontrib>Chan, Anthony W S</creatorcontrib><title>miR-196a Ameliorates Cytotoxicity and Cellular Phenotype in Transgenic Huntington's Disease Monkey Neural Cells</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>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. 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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.</description><subject>Age</subject><subject>Animals</subject><subject>Animals, Genetically Modified</subject><subject>Apoptosis</subject><subject>Biology and Life Sciences</subject><subject>Biomarkers</subject><subject>Brain research</subject><subject>Brain-derived neurotrophic factor</subject><subject>Cells (biology)</subject><subject>Cognitive ability</subject><subject>Cytotoxicity</subject><subject>Dehydrogenases</subject><subject>Disease Models, Animal</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genetic engineering</subject><subject>Genetics</subject><subject>High definition television</subject><subject>Humans</subject><subject>Huntington Disease - pathology</subject><subject>Huntington's disease</subject><subject>Huntingtons disease</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>MicroRNAs - 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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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>27631085</pmid><doi>10.1371/journal.pone.0162788</doi><tpages>e0162788</tpages><orcidid>https://orcid.org/0000-0002-3716-8179</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Age Animals Animals, Genetically Modified Apoptosis Biology and Life Sciences Biomarkers Brain research Brain-derived neurotrophic factor Cells (biology) Cognitive ability Cytotoxicity Dehydrogenases Disease Models, Animal Gene expression Genes Genetic aspects Genetic engineering Genetics High definition television Humans Huntington Disease - pathology Huntington's disease Huntingtons disease Medical research Medicine Medicine and Health Sciences MicroRNAs - physiology Mitochondria Mitochondria - metabolism Nervous system diseases Neural stem cells Neural Stem Cells - metabolism Neurodegenerative diseases Neurosciences Oxidative stress Pathogenesis Phenotype Polyglutamine Primates Progenitor cells Research and Analysis Methods Rodents Stem cells Studies Toxicity Trinucleotide repeat diseases |
| title | miR-196a Ameliorates Cytotoxicity and Cellular Phenotype in Transgenic Huntington's Disease Monkey Neural Cells |
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