2015 Fiscal Year Final Research Report
A novel therapeutic target for neurological disoders by inhibition of GAPDH aggregation
Project/Area Number |
25450428
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Veterinary medical science
|
Research Institution | Osaka Prefecture University |
Principal Investigator |
Nakajima Hidemitsu 大阪府立大学, 生命環境科学研究科(系), 准教授 (30405360)
|
Co-Investigator(Kenkyū-buntansha) |
KUWAMURA Mitsuru 大阪府立大学, 生命環境科学研究科・獣医学専攻, 准教授 (20244668)
|
Co-Investigator(Renkei-kenkyūsha) |
YUBA Eiji 大阪府立大学, 工学研究科, 助教 (80582296)
|
Project Period (FY) |
2013-04-01 – 2016-03-31
|
Keywords | 脳神経疾患 / GAPDH / アルツハイマー病 / 脳卒中 / 酸化ストレス / 創薬 / ペプチドミミック / 凝集阻害剤 |
Outline of Final Research Achievements |
Glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a homotetrameric protein that also mediates cell death under oxidative stresses. We previously reported that intermolecular disulfide-bonding GAPDH aggregates through oxidation of the active site cysteine (Cys-152) participate in oxidative stress-induced cell death. We also revealed that the active site cysteine-null GAPDH (C152A-GAPDH) rescues oxidative stress-induced neuronal cell death in a dominant negative manner via the formation of these hybrid tetramer both in vitro and in vivo. Here we report that this dominant negative C152A-GAPDH mutant against endogenous GAPDH aggregation in response to oxidative stress ameliorated neuronal cell death in neurological models using a specific inhibitor of GAPDH aggregation (GAI-X) exerted decrease of neurological dysfunctions. These findings provide a therapeutic avenue of new drug target for the brain damages such as Stroke and Alzheimer disease.
|
Free Research Field |
獣医薬理学
|