| Project/Area Number |
17591519
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Cerebral neurosurgery
|
|---|
| Research Institution | Kumamoto University |
|---|
Principal Investigator |
MORIOKA Motohiro Kumamoto University, Faculty of Medical and Pharaceutical Sciences, Assistant Professor, 医学部附属病院, 講師 (20295140)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KURATSU Jun-ichi Kumamoto University, Faculty of Medical and Pharaceutical Sciences, Professor, 大学院医学薬学研究部, 教授 (20145296)
KAI Yutaka Kumamoto University, Faculty of Medical and Pharaceutical Sciences, Assistant, 大学院医学薬学研究部, 助手 (30322308)
YANO Shigetoshi Kumamoto University, Faculty of Medical and Pharaceutical Sciences, Assistant, 医学部附属病院, 助手 (60332871)
|
|---|
| Project Period (FY) |
2005 – 2006
|
| Project Status |
Completed (Fiscal Year 2006)
|
| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2006: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2005: ¥2,000,000 (Direct Cost: ¥2,000,000)
|
|---|
| Keywords | brain ischemia / Tau factor / hyperphosphorylation / Vanadate / Apo-E / リン酸化反応 / 虚血性神経細胞死 |
|---|
| Research Abstract |
We examined the sequential phsopharylational state of tau factor in CA1 delayed neuronal cell death (DND) after transient forebrain ischemia The hyperphosphorylation at serine 199/202 of tau factor was found in CAI neuronal cell 12hr to 1.5 days after transient ischemia, whereas serine 398 showed no obvious change. These hyperphosphrylation was not found in the CA1 obtained ischemia-torelance nor in CA3 neuron where neuronal cell death did not occur. These data suggested that hyperphorylation of tau 199/202 serine was related to neuronal cell death.
Next, we examined which kinase played important role for tau hyperphosphrylation after ischemia We have injected several kinase inhibitor into animal lateral ventricle stereotactically after ischemia. According to inhibitor study, we concluded tha: cdk-5, Akt and GSK-3 kinases played important roles for tau hyperphosphorylation. Furthermore, calcineurin was suggested as an important phosphatase.
We have prepared recombinat human tau by molecular biological technique; normal human tau-40, and dephosphorylated form human tau-40 (serine was changed to alanine at 199/202), both was conjugated to TAT-protein. We have injected both protein, which was expressed in E.Coli and purified, into lateral ventricle and these animals were subjected to ischemic insult. Only dephosphrylated form tau showed inhibitory effect for ischemic neuronal cell death (DND). The hyperphosphry lation of tau factor was considered as one of major causes of Altzheimer disease. Our data showed common cell death pathway between Altzheimer disease and ischemic neuronal cell death and novel therapeutic strategy for ischemic neurc nal cell death.
We have reported vanadate have a protective effect for ischemic neuronal cell death. We examined the effect of vanadate for tau phosphorylation and obtained the data showed vanadate have an inhibitory effect against tau hyperphosphorylation.
|
