ADAM10/17活性调控在Aβ致神经小胶质细胞激活中的作用

The Role of ADAM10/17 Activity Regulation in Aβ-induced Neuroglial Activation

阿尔茨海默病(AD)是一种神经退行性疾病,严重影响老年患者的生活质量。AD最主要的致病机制是淀粉样β蛋白(Aβ)对神经细胞的损伤。Aβ前体淀粉样前体蛋白(APP)由β和γ剪切酶剪切而来,另外α剪切酶也可剪切APP,从而减少Aβ的产量。因此上调α剪切酶ADAM10/17的活性有可能成为AD的治疗策略之一。该研究实验数据证实,ADAM10/17不仅参与APP的剪切,还参与神经胶质细胞的激活和神经炎症反应;ADAM10/17可能参与胶质细胞炎症因子翻译后的修饰和剪切。该研究的结果为APPα剪切酶激活剂的研究提供了研究基础,在APPα剪切酶激活剂的研发过程中,不应只局限于神经细胞的作用,还必须考虑神经胶质细胞神经炎症的参与,以有效规避药物的不良反应。

AD(Alzheimer’s disease)is a neurodegenerative disease that seriously affects life quality of elderly patients.The most important pathogenic mechanism of AD is the damage of nerve cells by Aβ(amyloidβprotein).Aβis cleaved by its precursor APP(amyloid precursor protein)byβandγsecretase.αsecretase can cleave APP to reduce Aβproduction.Therefore,up-regulating the activity ofα-secretase ADAM10/17 may become one of the therapeutic strategies of AD.The experimental data of this study confirmed that ADAM10/17 was not only involved in the cleavage of APP,but also involved in the activation of glial cells and neuroinflammatory reactions.ADAM10/17 may be involved in the modification and cleavage of glial inflammatory factors after translation.The results of this study provide a basis for the study of APPα-secretase activator.In the development of APPα-secretase activator,it should not be limited to the role of nerve cells,but also the involvement of glial neuroinflammatory in order to achieve effective elimination of adverse drug reactions.