The Study of Cell Polarity, Movement and Unfolded Protein Phagocytosis in Brain Glial Cells

阿尔茨海默病(AD)是以细胞外淀粉样蛋白(Aβ，Aβ)纤维和小胶质细胞聚集为特征的疾病。近年来，由于小胶质细胞途径被认为是脑实质中清除Aβ的途径之一，Aβ的小胶质细胞吞噬作用引起了人们的极大兴趣。然而，小胶质细胞吞噬Aβ的机制尚不完全清楚，因此，本研究对此进行了研究。Aβ1-42(Aβ42)作用1min后，在小胶质细胞表面检测到β免疫反应。60min后，胞液小泡内可见明显的免疫反应。12h时，A-β-42纤维细胞吞噬延迟，形成一个大的吞噬杯。在吞噬过程中，小胶质细胞的形态迅速转变为阿米巴状。虽然神经性Wiskott-Aldrich综合征蛋白(N-WASP)和WASP相互作用SH3蛋白(WISH)均未与丝状肌动蛋白(F-Actin)共定位，但WASP家族Verprolin同源蛋白(WAVE)和rac1免疫反应与F-Actin共同定位于巨噬细胞小胶质细胞的板脂中。提示WAVE和RAC1参与了小胶质细胞吞噬Aβ42的过程。

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.