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
|
| Project Status |
Completed (Fiscal Year 2015)
|
| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
|---|
| 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 / アミロイド / 阻害剤 / ミトコンドリア / ＰＡＲＰ / 凝集 / 核移行 / 治療薬 |
|---|
| 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.
|
Report
(4 results)
Research Products
(14 results)
-
-
-
[Journal Article] Glyceraldehyde-3-phosphate Dehydrogenase Aggregates Accelerate Amyloid-β Amyloidogenesis in Alzheimer Disease.2015
Author(s)
Itakura, M., Nakajima, H., Kubo, T., Semi, Y., Kume, S., Higashida, S., Kaneshige, A., Kuwamura, M., Harada, N., Kita, A., Azuma, Y. T., Yamaji, R., Inui, T., Takeuchi, T.
-
Journal Title
J. Biol. Chem.
Volume: 290
Issue: 43
Pages: 26072-26087
DOI
Related Report
Peer Reviewed
-
[Journal Article] Role of Apoptosis Signal-regulating Kinase 1 (ASK1) as an activator of the GAPDH-Siah1 Stress-Signaling Cascade.2015
Author(s)
Tristan C.A., Ramos A., Shahani N., Emiliani F.E., Nakajima H., Noeh C.C., Kato Y., Takeuchi T., Noguchi T., Kadowaki H., Sedlak T.W., Ishizuka K., Ichijo H., Sawa, A.
-
Journal Title
The Journal of Biological Chemistry
Volume: 290
Issue: 1
Pages: 56-64
DOI
Related Report
Peer Reviewed / Open Access
-
[Journal Article] Nuclear-translocated glyceraldehyde-3-phosphate dehydrogenase promotes poly(ADP-ribose) polymerase-1 activation during oxidative/nitrosative stress in stroke.2015
Author(s)
Nakajima H, Kubo T, Ihara H, Hikida T, Danjo T, Nakatsuji M, Shahani N, Itakura M, Ono Y, Azuma Y, Inui T, Kamiya A, Sawa A, Takeuchi T
-
Journal Title
J. Biol. Chem.
Volume: VOL. 290
Issue: 23
Pages: 14493-14503
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
-
-
-
-
-
-
-
-
-
