Glial Cell Therapy Using Neuroprotective effects of Glia

最近的研究表明，内质网(ER)的长期功能障碍和/或应激可能参与了发病机制和神经退行性变。蛋白质错误折叠和聚集引起的疾病被称为构象疾病，包括阿尔茨海默病(AD)。AD的特征是细胞外淀粉样蛋白1-42(Aβ1-42，Aβ42)纤维和小胶质细胞聚集。了解Aβ42的产生和清除的平衡是阐明淀粉样斑块动态平衡的关键。我们最近发现，A GTP 42的小胶质细胞吞噬功能可能主要是通过维斯柯特-阿尔德里奇综合征蛋白家族的Verprolin同源蛋白(WAVE)和β结合蛋白Rac1的途径来驱动肌动蛋白细胞骨架的动态重组。此外，细胞外应激蛋白，如热休克蛋白-90(HSP90)，可促进Aβ42的吞噬作用。高迁移率族蛋白1抑制小胶质细胞对Aβ42的吞噬作用，并与Aβ42结合，稳定异构化。这些结果表明，Aβ42的小胶质细胞清除可能是研究AD治疗策略的另一种选择。此外，虽然大脑中动脉(MCA)闭塞导致大量神经元丢失，但脑室注射的小胶质细胞迁移到受损的脑实质，从而对抗局灶性脑缺血所致的神经变性。

Recent studies have indicated that prolonged dysfunction and/or stress in the endoplasmic reticulum (ER) may contribute to pathogenesis and neurodegeneration. The disorder caused by misfolding and aggregation of proteins has been referred to as conformational disease, including Alzheimer's disease (AD). AD is characterized by the accumulation of extracellular amyloid-β 1-42 (Aβ42) fibrils with microglia. Understanding the balance of production and clearance of Aβ42 is the key to elucidating amyloid plaque homeostasis. We have recently found that microglial phagocytosis of Aβ42 may be essentially driven by dynamic reorganization of the actin cytoskeleton through the pathway of the Wiskott-Aldrich syndrome protein family verprolin-homologous protein (WAVE) and GTP-binding protein Rac1. In addition, an extracellular stress protein, such as heat-shock protein-90 (Hsp90), enhanced Aβ42 phagocytosis. High mobility group box protein-1 (HMGB1) inhibited microglial phagocytosis of Aβ42, and it bound Aβ42 and stabilized the ologomerization. These results suggest that microglial clearance of Aβ42 may be another option for investigations in the search for a therapeutic strategy for AD. Furthermore, although occlusion of the middle cerebral artery (MCA) caused massive neuronal loss, intracerebroventricular-injected microglia migrated into brain damaged parenchyma and then protect against neurodegeneration by focal brain ischemia.