Viral delivery of miR-196a ameliorates the SBMA phenotype via the silencing of CELF2 |
| |
Authors: | Miyazaki Yu Adachi Hiroaki Katsuno Masahisa Minamiyama Makoto Jiang Yue-Mei Huang Zhe Doi Hideki Matsumoto Shinjiro Kondo Naohide Iida Madoka Tohnai Genki Tanaka Fumiaki Muramatsu Shin-ichi Sobue Gen |
| |
Affiliation: | Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan. |
| |
Abstract: | Spinal and bulbar muscular atrophy (SBMA) is an inherited neurodegenerative disorder caused by the expansion of the polyglutamine (polyQ) tract of the androgen receptor (AR-polyQ). Characteristics of SBMA include proximal muscular atrophy, weakness, contraction fasciculation and bulbar involvement. MicroRNAs (miRNAs) are a diverse class of highly conserved small RNA molecules that function as crucial regulators of gene expression in animals and plants. Recent functional studies have shown the potent activity of specific miRNAs as disease modifiers both in vitro and in vivo. Thus, potential therapeutic approaches that target the miRNA processing pathway have recently attracted attention. Here we describe a novel therapeutic approach using the adeno-associated virus (AAV) vector–mediated delivery of a specific miRNA for SBMA. We found that miR-196a enhanced the decay of the AR mRNA by silencing CUGBP, Elav-like family member 2 (CELF2). CELF2 directly acted on AR mRNA and enhanced the stability of AR mRNA. Furthermore, we found that the early intervention of miR-196a delivered by an AAV vector ameliorated the SBMA phenotypes in a mouse model. Our results establish the proof of principle that disease-specific miRNA delivery could be useful in neurodegenerative diseases. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|