2005 Fiscal Year Final Research Report Summary
Investigation of molecular mechanisms for common diseases caused by aging and oxidative stress and development of drug candidates aiming the molecular targets
| Project/Area Number |
15390029
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Biological pharmacy
|
|---|
| Research Institution | Kumamoto University |
|---|
Principal Investigator |
NAKAYAMA Hitoshi Kumamoto University, Graduate School of Medical and Pharmaceutical Sciences, Professor, 大学院・医学薬学研究部, 教授 (70088863)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KUNIYASU Akihiko Kumamoto University, Graduate School of Medical and Pharmaceutical Sciences, Associate Professor, 大学院・医学薬学研究部, 助教授 (90241348)
ISHIZUKA Tadao Kumamoto University, Graduate School of Medical and Pharmaceutical Sciences, Associate Professor, 大学院・医学薬学研究部, 助教授 (60176203)
KAWAHARA Kohichi Kumamoto University, Graduate School of Medical and Pharmaceutical Sciences, Assistant Professor, 大学院・医学薬学研究部, 助手 (10347015)
MIYAZAKI Akira Showa University, School of Medicine, Professor, 医学部, 教授 (70253721)
|
|---|
| Project Period (FY) |
2003 – 2005
|
| Keywords | scavenger receptors / adipocytes / microglia / Alzheimer's disease / β-amyloid peptide / clearance |
|---|
| Research Abstract |
In this project we aim to investigate the molecular mechanisms for adipocytokine production from adipocytes and clearance of β-amyloid peptide in microglia, which apply to develop drug candidates aiming the molecular targets. During the passed three years, we have obtained several novel findings and drug candidates as follows. (1)Production of some adipocytokines including resistin increased by stimulation of ox-LDL via translation modulated mechanism. (2)We found a novel clearance mechanism of oligomeric β-amyloid peptides, which is induced selectively in type-2 microglia by IL-4 stimulation. (3)The clearance mechanism was proved to induce in vivo using transgenic AD model mice. We also found that some compounds of low molecular weight are able to induce the clearance mechanism. (4)We are succeeded in generating specific monoclonal antibodies to discriminate type-1 and type-2 microglia (Patent is applied.)
All the results described above are more than we expected, and they are very promising to create new drugs for recovering from Alzheimer's disease, in particular.
|
