MiR-196a ameliorates phenotypes of huntington disease in cell, transgenic mouse, and induced pluripotent stem cell models

Pei Hsun Cheng, Chia Ling Li, Yu Fan Chang, Shaw Jeng Tsai, Yen Yu Lai, Anthony W.S. Chan, Chuan Mu Chen, Shang Hsun Yang

研究成果: Article同行評審

85 引文 斯高帕斯(Scopus)

摘要

Huntington disease (HD) is a dominantly inherited neurodegenerative disorder characterized by dysregulation of various genes. Recently, microRNAs (miRNAs) have been reported to be involved in this dysregulation, suggesting that manipulation of appropriate miRNA regulation may have a therapeutic benefit. Here, we report the beneficial effects of miR-196a (miR196a) on HD in cell, transgenic mouse models, and human induced pluripotent stem cells derived from one individual with HD (HD-iPSCs). In the in vitro results, a reduction of mutant HTT and pathological aggregates, accompanying the overexpression of miR-196a, was observed in HD models of human embryonic kidney cells and mouse neuroblastoma cells. In the in vivo model, HD transgenic mice overexpressing miR-196a revealed the suppression of mutant HTT in the brain and also showed improvements in neuropathological progression, such as decreases of nuclear, intranuclear, and neuropil aggregates and late-stage behavioral phenotypes. Most importantly, miR-196a also decreased HTT expression and pathological aggregates when HD-iPSCs were differentiated into the neuronal stage. Mechanisms of miR-196a in HD might be through the alteration of ubiquitin-proteasome systems, gliosis, cAMP response element-binding protein pathway, and several neuronal regulatory pathways in vivo. Taken together, these results show that manipulating miR-196a provides beneficial effects in HD, suggesting the potential therapeutical role of miR-196a in HD.

原文English
頁(從 - 到)306-312
頁數7
期刊American Journal of Human Genetics
93
發行號2
DOIs
出版狀態Published - 2013 8月 8

All Science Journal Classification (ASJC) codes

  • 遺傳學
  • 遺傳學(臨床)

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