Involvement of Wiskott-Aldrich Syndrome Protein Family Verprolin-Homologous Protein (WAVE) and Rac1 in the Phagocytosis of Amyloid-β(1 – 42) in Rat Microglia

Journal of Pharmacological Sciences

Peter J. Gebicke-Haerter²  Keiichi Shibagaki¹  Tadaomi Takenawa⁴  Daiju Tsuchiya¹  Takashi Taniguchi¹  Hiroaki Miki⁴  Kazuyuki Takata¹  Shun Shimohama³  Yoshihisa Kitamura¹ 

[1] Department of Neurobiology, Kyoto Pharmaceutical University;Department of Psychopharmacology, Central Institute of Mental Health;Department of Neurology, Graduate School of Medicine, Kyoto University;Division of Cancer Genomics, Institute of Medical Science, University of Tokyo

关键词: Wiskott-Aldrich syndrome protein family verprolin-homologous protein (WAVE);    Rac1;    amyloid-β(1 – 42);    microglial phagocytosis;    Alzheimer’s disease;   

DOI  :  10.1254/jphs.92.115

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(38)Cited-By(13)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 Aβ(1 – 42) (Aβ42), Aβ immunoreactivity was detected at the cell surface of microglia. After 1 h, marked immunoreactivity was observed in the cytosolic vesicles. At 12 h, 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.

【 授权许可】

Unknown