Research of signal transduction to neuronal degeneration mediated by tau-kinases complex in dementia
| Project/Area Number |
18590939
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Neurology
|
|---|
| Research Institution | Kobe University |
|---|
Principal Investigator |
KAWAMATA Toshio Kobe University, School of Medicine, Department of Health Sciences, Professor (70214690)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
MAEDA Kiyoshi Kobe University, Graduate School of Medicine, Professor (80116251)
ONO Yoshitaka Kobe University, Biosignal Research Center, Professor (10243297)
MUKAI Hideyuki Kobe University, Biosignal Research Center, Associate Professor (80252758)
TAKAHASHI Mikiko Kobe University, Biosignal Research Center, Lecturer (90324938)
|
|---|
| Project Period (FY) |
2006 – 2007
|
| Project Status |
Completed (Fiscal Year 2007)
|
| Budget Amount *help |
¥3,920,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥420,000)
Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2006: ¥2,100,000 (Direct Cost: ¥2,100,000)
|
|---|
| Keywords | Dementia / Alzheimer disease / Tau / Protein kinase / Protein / Neuron / Degeneration / Signal transduction |
|---|
| Research Abstract |
Neuronal localization of two large scaffold proteins interacting with some protein kineses and phosphateses, which phosphorylate or dephosphorylate tau protein directly, was studied to identify the pathology underlying neuronal death in the brain tissues of the patients with degenerative dementia including Alzheinier's disease (AD) and frontotanporal dementia (FTD).
Morphological colocalization of one platform protein but not of another molecule both with the kinases such as PKN, PKC, PKA and casein kinase 1δ and with the phoshatases such as PP1, PP2A and PP2B was found in primary cultured neurons and in neurons of the brains from mice, rats, human controls and the demented patients. Subcellular localizations of the complex was seen in the perinuclear cytoplasm and the proximal neurites of control neurons. By contrast, it was accumulated in intracellular neurofibrillary tangles and degenerative neurites in AD brains, and also accumulated in ballooned neurons in FTD brains. In addition, the interaction of a FK-bincling protein, which is known to be associated with the conformational modification or the transport of cellular proteins and is reported to interact with the intracellular domain of amyloid precursor protein, was identified with the intraneuronal tangles in AD brains. Colocalization of an important enzyme in sphingolipid biosynthesis with tangles was also found in AD brains. Moreover, we reported the cognitive changes in the patients with Parkinson's disease, and the altered expression of a novel susceptibility gene in the schizophrenia patients with cognitive symptoms.
Thus, our results suggest that a specific role of a scaffold protein with tau-kinases, tau-phosphatases and their interacting molecules in damaged neurons in the dementia including AD and FTD.
|
Report
(3 results)
Research Products
(7 results)
-
-
-
[Journal Article] Expression of Kruppel-like factor 5 gene in human brain and association of the gene with the susceptibility to schizophrenia2008
Author(s)
Masaya, Yanagi, Takeshi, Hashimoto, Noboru, Kitamura, Masaaki, Fukutake, Osamu, Konmre, Naoki, Nishiguchi, Toshio, Kawamata, Kiyoshi, Maeda, Osamu, Shirakawa
-
Journal Title
Schizophrenia Research 100(1-3)
Pages: 291-301
Description
「研究成果報告書概要(欧文)」より
Related Report
-
-
-
[Journal Article] Investigation of new candidate genes for schizophrenia2006
Author(s)
Masaya, Yanagi, Takeshi, Hashimoto, Noboru, Kitamura, Masaaki, Fukutake, Huxing, Cui, Naoki, Nishiguchi, Toshio, Kawamata, Osamu, Shirakawa, Kiyoshi, Maeda
-
Journal Title
Annual Report of Mitsubishi Pharma Research Foundation 38
Pages: 105-108
Description
「研究成果報告書概要(欧文)」より
Related Report
-
