Neuroinflammation is a critical mechanism responsible for the progression of Alzheimer's disease (AD). Recent studies reveal that Hippo/Yes-associated protein (YAP) signaling pathway is highly associated with a series of inflammation-related disorders. Glial cell line-derived neurotrophic factor (GDNF), with its neurotrophic and anti-apoptotic functions for nervous system, has been demonstrated to decrease the expression of proinflammatory mediators. Here we investigated whether Hippo/YAP signaling may affect amyloid-β (Aβ)-induced proinflammatory cytokine production in microglial cells and explored its relationship with the anti-inflammation function of GDNF. The results showed that Aβ induced a decrease in the expression of YAP in microglia cells. YAP agonist XMU-MP-1 or its overexpression in microglial cells caused decreased expression of proinflammatory cytokines, whereas YAP antagonist Verteporfin or knockdown of YAP had the opposite effect. Treatment with GDNF resulted in upregulation of YAP expression and reduced the production of proinflammatory cytokines. Meanwhile YAP knockdown weakened the function of GDNF in microglial cells. In conclusion, Hippo/YAP pathway plays a critical role in effect of GDNF against Aβ-induced inflammatory response in microglia. Targeting GDNF or Hippo/YAP signaling may be promising therapeutic approach for the treatment of AD.

中文翻译：

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Hippo / YAP途径在GDNF对抗小胶质细胞中Aβ诱导的炎症中起关键作用。

神经炎症是导致阿尔茨海默氏病（AD）进展的关键机制。最近的研究表明，河马/是相关蛋白（YAP）信号通路与一系列炎症相关疾病高度相关。胶质细胞源性神经营养因子（GDNF）具有神经系统的神经营养和抗凋亡功能，已被证明可减少促炎性介质的表达。在这里，我们调查了河马/ YAP信号是否可能影响小胶质细胞中淀粉样β（Aβ）诱导的促炎细胞因子的产生，并探讨了它与GDNF的抗炎功能的关系。结果表明，Aβ诱导了小胶质细胞中YAP表达的降低。YAP激动剂XMU-MP-1或其在小胶质细胞中的过表达导致促炎细胞因子的表达降低，而YAP拮抗剂Verteporfin或YAP的抑制作用则相反。GDNF治疗导致YAP表达上调并减少了促炎细胞因子的产生。同时，YAP敲低削弱了小胶质细胞中GDNF的功能。总之，Hippo / YAP途径在GDNF对抗小胶质细胞中Aβ诱导的炎症反应中起关键作用。靶向GDNF或Hippo / YAP信号传导可能是用于治疗AD的有前途的治疗方法。同时，YAP敲低削弱了小胶质细胞中GDNF的功能。总之，Hippo / YAP途径在GDNF对抗小胶质细胞中Aβ诱导的炎症反应中起关键作用。靶向GDNF或Hippo / YAP信号传导可能是用于治疗AD的有前途的治疗方法。同时，YAP敲低削弱了小胶质细胞中GDNF的功能。总之，Hippo / YAP途径在GDNF对抗小胶质细胞中Aβ诱导的炎症反应中起关键作用。靶向GDNF或Hippo / YAP信号传导可能是用于治疗AD的有前途的治疗方法。