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Abstract：
BACKGROUND: Neuroinflammation is a characteristic pathological change of Alzheimer\'s Diseases (AD). Microglia have been reported to participate in inflammatory responses within the central nervous system. However, the mechanism of microglia released exosome (EXO) contribute to communication within AD microenvironment remains obscure.
METHODS: The interaction between microglia and AD was investigated in vitro and in vivo. RNA-binding protein immunoprecipitation (RIP) was used to investigate the mechanisms of miR-223 and YB-1. The association between microglia derived exosomal YB-1/miR-223 axis and nerve cell damage were assessed using Western blot, immunofluorescence, RT-PCR, ELISA and wound healing assay.
RESULTS: Here, we reported AD model was responsible for the M1-like (pro-inflammatory) polarization of microglia which in turn induced nerve cell damage. While M2-like (anti-inflammatory) microglia could release miR-223-enriched EXO which reduced neuroinflammation and ameliorated nerve damage in AD model in vivo and in vitro. Moreover, YB-1 directly interacted with miR-223 both in cell and EXO, and participated in microglia exosomal miR-223 loading.
CONCLUSIONS: These results indicate that anti-inflammatory microglia-mediated neuroprotection form inflammatory damage involves exporting miR-223 via EXO sorted by YB-1. Consequently, YB-1-mediated microglia exosomal sorting of miR-223 improved the nerve cell damage repair, representing a promising therapeutic target for AD.
METHODS: The interaction between microglia and AD was investigated in vitro and in vivo. RNA-binding protein immunoprecipitation (RIP) was used to investigate the mechanisms of miR-223 and YB-1. The association between microglia derived exosomal YB-1/miR-223 axis and nerve cell damage were assessed using Western blot, immunofluorescence, RT-PCR, ELISA and wound healing assay.
RESULTS: Here, we reported AD model was responsible for the M1-like (pro-inflammatory) polarization of microglia which in turn induced nerve cell damage. While M2-like (anti-inflammatory) microglia could release miR-223-enriched EXO which reduced neuroinflammation and ameliorated nerve damage in AD model in vivo and in vitro. Moreover, YB-1 directly interacted with miR-223 both in cell and EXO, and participated in microglia exosomal miR-223 loading.
CONCLUSIONS: These results indicate that anti-inflammatory microglia-mediated neuroprotection form inflammatory damage involves exporting miR-223 via EXO sorted by YB-1. Consequently, YB-1-mediated microglia exosomal sorting of miR-223 improved the nerve cell damage repair, representing a promising therapeutic target for AD.
摘要：
背景：神经炎症是阿尔茨海默病（AD）的特征性病理改变。已报道小胶质细胞参与中枢神经系统内的炎症反应。然而,小胶质细胞外泌体(EXO)对AD微环境内通讯的作用机制尚不清楚。
方法：在体外和体内研究了小胶质细胞与AD之间的相互作用。RNA结合蛋白免疫沉淀（RIP）用于研究miR-223和YB-1的机制。使用Westernblot评估小胶质细胞来源的外泌体YB-1/miR-223轴与神经细胞损伤之间的关联。免疫荧光，RT-PCR,ELISA和伤口愈合测定。
结果：这里，我们报道AD模型是导致小胶质细胞M1样(促炎)极化的原因,而后者又诱导神经细胞损伤.而M2样（抗炎）小胶质细胞可以释放富含miR-223的EXO，从而在体内和体外减轻AD模型中的神经炎症并改善神经损伤。此外，YB-1在细胞和EXO中直接与miR-223相互作用，并参与小胶质细胞外泌体miR-223的装载。
结论：这些结果表明，抗炎小胶质细胞介导的神经保护形成炎性损伤涉及通过YB-1分类的EXO输出miR-223。因此,YB-1介导的小胶质细胞外泌体分选miR-223促进神经细胞损伤修复,代表了AD的有希望的治疗目标。
方法：在体外和体内研究了小胶质细胞与AD之间的相互作用。RNA结合蛋白免疫沉淀（RIP）用于研究miR-223和YB-1的机制。使用Westernblot评估小胶质细胞来源的外泌体YB-1/miR-223轴与神经细胞损伤之间的关联。免疫荧光，RT-PCR,ELISA和伤口愈合测定。
结果：这里，我们报道AD模型是导致小胶质细胞M1样(促炎)极化的原因,而后者又诱导神经细胞损伤.而M2样（抗炎）小胶质细胞可以释放富含miR-223的EXO，从而在体内和体外减轻AD模型中的神经炎症并改善神经损伤。此外，YB-1在细胞和EXO中直接与miR-223相互作用，并参与小胶质细胞外泌体miR-223的装载。
结论：这些结果表明，抗炎小胶质细胞介导的神经保护形成炎性损伤涉及通过YB-1分类的EXO输出miR-223。因此,YB-1介导的小胶质细胞外泌体分选miR-223促进神经细胞损伤修复,代表了AD的有希望的治疗目标。
