| Project/Area Number |
23390231
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Neurology
|
|---|
| Research Institution | Nagoya University |
|---|
Principal Investigator |
ADACHI Hiroaki 名古屋大学, 医学(系)研究科(研究院), 寄附講座准教授 (40432257)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SOBUE Gen 名古屋大学, 医学系研究科, 教授 (20148315)
KOIKE Haruki 名古屋大学, 医学部附属病院, 病院講師 (80378174)
TANAKA Fumiaki 横浜市立大学, 医学系研究科, 教授 (30378012)
|
|---|
| Research Collaborator |
MIYAZAKI Yu 名古屋大学, 医学系研究科, 客員研究者
|
|---|
| Project Period (FY) |
2011-04-01 – 2014-03-31
|
| Project Status |
Completed (Fiscal Year 2013)
|
| Budget Amount *help |
¥19,370,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥4,470,000)
Fiscal Year 2013: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2012: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2011: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
|
|---|
| Keywords | 球脊髄性筋萎縮症 / アンドロゲンレセプター / CAGリピート / miRNA / CELF2 / 運動ニューロン病 / 神経変性疾患 / miR-196a / ポリグルタミン病 / Dicer / AAVベクター / アンドロゲン受容体 / トランスジェニックマウス |
|---|
| Research 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. 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. We demonstrated 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.
|
