상위피인용논문
- 조회973
Abstract
Soon-Tae Leea, b, 1, Kon Chua, b, 1, Woo-Seok Ima, Hye-Jin Yoona, Ji-Yeon Ima, Jung-Eun Parka, Ki-Ho Parkc, Keun-Hwa Junga, b, Sang Kun Leea, b, Manho Kima, b, Jae-Kyu Roha, b
a Neurodegeneration Research Laboratory, Department of Neurology, Clinical Research Institute, Seoul National University Hospital, Seoul, South Korea
b Program in Neuroscience, Neuroscience Research Institute of SNUMRC, Seoul National University, Seoul, South Korea
c Quantitative PCR & Genomics Laboratory, Clinical Research Institute, Seoul National University Hospital, Seoul, South Korea
Corresponding author. Department of Neurology, Seoul National University Hospital, 101, Daehangno, Jongno-gu, Seoul, 110-744, South Korea
1 These two authors contributed equally to this work.
Abstract
Huntington's disease (HD) is a genetic neurodegenerative disease caused by abnormal CAG expansion. MicroRNAs (miRNAs) are short RNA molecules regulating gene expression, and are implicated in a variety of diseases including HD. However, the profiles and regulation of miRNAs in HD are not fully understood. Here, we analyzed the miRNA expression and miRNA regulators in two transgenic models of HD, YAC128 and R6/2 mice, and in a 3-nitropropionic acid (3NP)-induced striatal degeneration rat model. After characterizing the phenotypes by behavioral tests and histological analyses, we profiled striatal miRNAs using a miRNA microarray and we measured the key molecules involved in miRNA biogenesis and function. YAC128 mice showed upregulation-dominant miRNA expressions at 5 months and downregulation-dominant expressions at 12 months. Concomitantly, the expressions of Drosha-DGCR8, Exportin-5, and Dcp1 were increased at 5 months, and the expression of Dicer was decreased at 12 months. In 10-week-old R6/2 mice, downregulation was dominant in the miRNA expressions and the level of Drosha decreased concomitantly. Nine miRNAs (miR-22, miR-29c, miR-128, miR-132, miR-138, miR-218, miR-222, miR-344, and miR-674*) were commonly down-regulated in both the 12-month-old YAC128 and 10-week-old R6/2 mice. Meanwhile, 3NP rats showed dynamic changes in the miRNA profiles during disease development and a few miRNAs with altered expression. Our results show that transgenic HD mice have abnormal miRNA biogenesis. This information should aid in future studies on therapeutic application of miRNAs in HD.
논문정보
- Research article
- 2011년 01월 (BRIC 등록일 2017-03-31)
- 국내 연구진
- 의약학 > 신경의학
- 120회 이상 인용된 논문
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