School of Medicine and Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Department of Pharmacology, Nanjing Medical University, Jiangsu 211166, China.
Biomed Pharmacother. 2023 Dec;168:115735. doi: 10.1016/j.biopha.2023.115735. Epub 2023 Oct 16.
α-Synuclein is a member of a protein of synucleins, which is a presynaptic neuron protein. It is usually highly expressed in the brain and participates in the formation and transmission of nerve synapses. It has been reported that abnormal aggregation of α-Syn can induce the activation of NLRP3 inflammasome in microglia, increase the production of IL-1β, and aggravate neuroinflammation. Therefore, it is recognized as one of the important factors leading to neuroinflammation in Parkinson's disease. In this paper, we aimed to explore the influence of post-translational modification of α-Syn on its pathological aggregation and summarize various pathways that activate NLRP3 triggered by α-Syn and targeted therapeutic strategies, which provided new insights for further exploring the origin and targeted therapy of Parkinson's disease.
α-突触核蛋白是突触核蛋白家族的一员，它是一种突触前神经元蛋白。它通常在大脑中高度表达，并参与神经突触的形成和传递。有报道称，α-突触核蛋白的异常聚集可诱导小胶质细胞中 NLRP3 炎性体的激活，增加 IL-1β 的产生，并加重神经炎症。因此，它被认为是导致帕金森病神经炎症的重要因素之一。本文旨在探讨 α-突触核蛋白翻译后修饰对其病理性聚集的影响，并总结激活 α-突触核蛋白触发的 NLRP3 的各种途径和靶向治疗策略，为进一步探讨帕金森病的发病机制和靶向治疗提供新的思路。
