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低效的溶酶体降解是多种脑部疾病发展的中心环节,但其具体机制及参与的细胞种类仍不清楚。既往研究显示,星形胶质细胞大量吞噬死亡的细胞,但将这些吞噬的物质储存在细胞内而不是进行降解。本研究对星形胶质细胞降解消化功能减弱的原因进行研究,并探索增强星形胶质细胞降解消化功能的方法。结果显示,长期存在于吞噬泡周围的肌动环阻碍了溶酶体的吞噬溶解作用。此外,Rab27a蛋白可以通过Nox2减少溶酶体的酸化,而星形胶质细胞高表达Rab27a蛋白,阻碍抗原呈递。本研究还发现,Nox2与星形胶质细胞摄取的物质共定位,且表达主要组织相容性复合体II,提示这可能影响星形胶质细胞内的抗原呈递。使用酸化纳米粒子对星形胶质细胞溶酶体进行长时间的酸化处理,能增加星形胶质细胞对所摄取物质和死亡细胞的消化。但随着酸化时间的延长,星形胶质细胞的消化能力再次回复到较低水平,提示随着酸化作用的增强,细胞的对抗酸化的通路也相应增强了。
Inefficient lysosomal degradation is central to the development of a variety of brain diseases, but the exact mechanisms and cell types involved remain unclear. Previous studies have shown that astrocytes engulf dead cells in large numbers, but store these phagocytic substances in cells instead of degrading. In this study, the reasons for the weakened digestive function of astrocytes were studied and the methods to enhance the degradation and digestion of astrocytes were explored. The results show that long-term presence of phagosomes around the motor loop hinders the phagolysis lysosomal dissolution. In addition, Rab27a reduces lysosomal acidification with Nox2, whereas astrocytes overexpress Rab27a, hindering antigen presentation. This study also found that Nox2 co-localized with astrocyte uptake and expressed major histocompatibility complex II, suggesting that this may affect antigen presentation in astrocytes. Long-term acidification of astroglial lysosomes with acidified nanoparticles can increase the astroglial digestion of uptake and dead cells. But with the prolongation of acidification time, the astrocyte digestion ability returned to a lower level again, suggesting that with the enhancement of acidification, the cell’s anti-acidification pathway also increased accordingly.