2003 Fiscal Year Final Research Report Summary
Study of signal transduction to neuronal death through tau phosphorylation
| Project/Area Number |
14370207
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Kobe University |
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Principal Investigator |
KAWAMATA Toshio Kobe University, Graduate School of Medicine, Professor, 医学部, 教授 (70214690)
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| Co-Investigator(Kenkyū-buntansha) |
MUKAI Hideyuki Kobe Univ., Grad.Sch.of Sci.and Tech., Associate Professor, 大学院・自然科学研究科, 助教授 (80252758)
ONO Yoshitaka Kobe University, Biosignal Research Center, Professor, バイオシグナル研究センター, 教授 (10243297)
MAEDA Kiyoshi Kobe University, Graduate School of Medicine, Professor, 医学部, 教授 (80116251)
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| Project Period (FY) |
2002 – 2003
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| Keywords | Alzheimer disease / Neuronal death / Tau / Phosphorylation / Protein kinase / Protein phosphatase / Signal transduction |
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| Research Abstract |
Neuronal mechanisms mediating interaction of protein kinases and phosphatases around intracellular neurofibrillary tangles (NFTs) were studied to determine the implication of tau phosphorylation in neuronal death seen in brain tissues of the patients with Alzheimer disease (AD). We have investigated a role for a protein kinase PKN, a fatty acid-activated serine/threonine kinase with a catalytic domain homologous to that of protein kinase C family and a direct target for Rho, and provided evidences that PKN is enriched in a subset of endoplasmic reticulum (ER) and ER-derived vesicles associated with NFTs in AD-affected neurons. We now found a protein which interacted with the regulatory region of PKN. We characterized and revealed that the molecule interacts with some protein kinases, including protein kinase C, protein kinase A, and casein kinase CK1, as well as PKN, and also interacts with some protein phosphatases such as protein phosphatase 1 and protein phosphatase 2A. These kinases or phosphatases are all known to phosphorylate or dephosphorylate tau protein directly. Then, we raised a specific antibody against this molecule and localized it in rat and human brains. The expression was almost restricted to neurons with vesicular profiles in the cytoplasm. Immunoelectron microscopic study revealed that the interacting protein was accumulated in small vesicles localized around NFTs and within degenerative neurites in AD brain tissues. Thus, our results suggest a specific role for the interacting protein in NFT formation and neurodegeneration in AD damaged neurons.
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Research Products
(4 results)
