| Project/Area Number |
14572082
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Kyoto Pharmaceutical University |
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Principal Investigator |
KITAMURA Yoshihisa Kyoto Pharmaceutical University, Pharmaceutical Sciences, Neurobiology, Associate Professor, 薬学部・病態生理学, 助教授 (60195295)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Microglia / Amyloid-β(1-42) / Phagocytosis / Actin reorganization / WASP family / Small GTPases / Amyloid-β clearance / Alzheimer's disease / アストロサイト |
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| Research Abstract |
Alzheimer's disease (AD) is characterized by the accumulation of extracellular amyloid-β (Aβ) fibrils with microglia. Recently, there has been great interest in the microglial phagocytosis of Aβ, because the microglial pathway is considered to be one of the Aβ clearance pathways in the brain parenchyma. However, the mechanism of microglial phagocytosis of Aβ is not fully understood and, thus, was investigated in this study. At one minute after exposure to Aβ1-42 (Aβ42), Aβ immunoreactivity was detected at the cell surface of microglia. After 60min, marked immunoreactivity was observed in the cytosolic vesicles. At 12h, delayed phagocytosis of fibrillar Aβ42 was also observed with the formation of a large phagocytic cup. The microglial cell shape rapidly changed to an ameboid form during the process of phagocytosis. Although neither neural Wiskott-Aldrich syndrome protein (N-WASP) nor WASP interacting SH3 protein (WISH) immunoreactivity was co-localized with filamentous actin (F-actin) distribution, both WASP family verprolin-homologous protein (WAVE) and Rac1 immunoreactivity was co-localized with F-actin in the lamellipodia of phogocytic microglia. These results suggest that WAVE and Rac1 participate in the phagocytosis of Aβ42 by microglia.
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