Jiang Xiuli, Wang Xiaoli, Tuo Miao, Ma Jiangnan, Xie Anmu
Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, China.
Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, China.
Neurosci Lett. 2018 Apr 13;672:65-69. doi: 10.1016/j.neulet.2018.02.049. Epub 2018 Mar 21.
Receptor for advanced glycation end products (RAGE) is a multiligand receptor belonging to the immunoglobulin superfamily and plays crucial roles in the development of many human diseases such as neurodegenerative diseases, diabetes, cardiovascular diseases, osteoarthritis and cancer. RAGE involves in a number of cell processes such as neuroinflammation, apoptosis, proliferation and autophagy. In CNS, RAGE was primarily expressed in neurons, microglia and vascular endothelial cells. Interacting with ligands, RAGE induces a series of signal transduction cascades and leads to the activation of transcription factor NF-κB as well as increased expression of cytokines like TNF-α, IL-1. Moreover, binding to RAGE can also stimulate the generation of reactive oxygen species (ROS), which is implicated in neuron death. It was reported that RAGE were highly expressed in PD patients when compared to age-matched controls. And RAGE ablation protected nigral dopaminergic neurons against cell death in MPTP treated mice. Here we review this article to elucidate the role of RAGE in PD pathogenesis and highlight the anti-RAGE strategies in the treatment of PD.
晚期糖基化终末产物受体（RAGE）是一种属于免疫球蛋白超家族的多配体受体，在许多人类疾病的发展中起着关键作用，如神经退行性疾病、糖尿病、心血管疾病、骨关节炎和癌症。RAGE参与多种细胞过程，如神经炎症、细胞凋亡、增殖和自噬。在中枢神经系统中，RAGE主要在神经元、小胶质细胞和血管内皮细胞中表达。与配体相互作用时，RAGE会诱导一系列信号转导级联反应，导致转录因子NF-κB的激活以及细胞因子如TNF-α、IL-1表达的增加。此外，与RAGE结合还可刺激活性氧（ROS）的产生，这与神经元死亡有关。据报道，与年龄匹配的对照组相比，RAGE在帕金森病患者中高度表达。并且RAGE基因敲除可保护黑质多巴胺能神经元免受MPTP处理小鼠中的细胞死亡。在此，我们回顾本文以阐明RAGE在帕金森病发病机制中的作用，并强调抗RAGE策略在帕金森病治疗中的应用。
