Abstract：
In Alzheimer\'s disease, the microtubule-associated protein, Tau misfolds to form aggregates and filaments in the intra- and extracellular region of neuronal cells. Microglial cells are the resident brain macrophage cells involved in constant surveillance and activated by the extracellular deposits. Purinergic receptors are involved in the chemotactic migration of microglial cells towards the site of inflammation. From our recent study, we have observed that the microglial P2Y12 receptor is involved in phagocytosis of full-length Tau species such as monomers, oligomers and aggregates by actin-driven chemotaxis. This study shows the interaction of repeat-domain of Tau (TauRD) with the microglial P2Y12 receptor and the corresponding residues for interaction have been analyzed by various in-silico approaches. In the cellular studies, TauRD was found to interact with microglial P2Y12R and induces its cellular expression confirmed by co-immunoprecipitation and western blot analysis. Furthermore, the P2Y12R-mediated TauRD internalization has demonstrated activation of microglia with an increase in the Iba1 level, and TauRD becomes accumulated at the peri-nuclear region for the degradation.
摘要：
在阿尔茨海默病中，微管相关蛋白，Tau错误折叠以在神经元细胞的内部和细胞外区域形成聚集体和细丝。小胶质细胞是参与持续监视并被细胞外沉积物激活的常驻脑巨噬细胞。嘌呤能受体参与小胶质细胞向炎症部位的趋化性迁移。从我们最近的研究来看,我们观察到，小胶质细胞P2Y12受体参与吞噬作用的全长Tau物种，如单体，肌动蛋白驱动的趋化性的寡聚物和聚集体。这项研究表明，Tau的重复结构域（TauRD）与小胶质细胞P2Y12受体的相互作用以及相应的相互作用残基已通过各种计算机模拟方法进行了分析。在细胞研究中，发现TauRD与小胶质细胞P2Y12R相互作用，并诱导其细胞表达，通过免疫共沉淀和蛋白质印迹分析证实。此外，P2Y12R介导的TauRD内化已证明小胶质细胞的激活与Iba1水平的增加，和TauRD积累在核周区域进行退化。
