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

阿尔茨海默病（Alzheimer's disease，AD）是一种以小胶质细胞聚集于细胞外的β淀粉样蛋白（amyloid-β，Aβ）纤维为特征的疾病。近年来，由于小胶质细胞途径被认为是脑实质中Aβ清除途径之一，因此小胶质细胞对Aβ的吞噬作用引起了人们极大的兴趣。然而，小胶质细胞吞噬Aβ的机制尚未完全了解，因此在本研究中进行了研究。Aβ1-42（Aβ42）作用1 min后，小胶质细胞表面可见Aβ免疫反应阳性细胞。60分钟后，在胞质小泡中观察到显著的免疫反应性。12 h时，Aβ42纤维状吞噬延迟，吞噬杯形成。在吞噬过程中，小胶质细胞的形状迅速转变为阿米巴样。虽然神经Wiskott-Aldrich综合征蛋白（N-WASP）和WASP相互作用SH 3蛋白（WISH）免疫反应性与丝状肌动蛋白（F-actin）分布均不共定位，但WASP家族verprolin同源蛋白（WAVE）和Rac 1免疫反应性均与F-actin共定位于吞噬细胞小胶质细胞的板状伪足中。这些结果表明WAVE和Rac 1参与了小胶质细胞对Aβ42的吞噬作用。

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.