Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai, 201318, China.
Center for Clinical and Translational Medicine, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, China.
Neurosci Bull. 2023 May;39(5):832-844. doi: 10.1007/s12264-023-01023-y. Epub 2023 Feb 9.
Parkinson's disease (PD) is a common neurodegenerative disorder caused by the loss of dopamine neurons in the substantia nigra and the formation of Lewy bodies, which are mainly composed of alpha-synuclein fibrils. Alpha-synuclein plays a vital role in the neuroinflammation mediated by the nucleotide-binding oligomerization domain-, leucine-rich repeat-, and pyrin domain-containing protein 3 (NLRP3) inflammasome in PD. A better understanding of the NLRP3 inflammasome-mediated neuroinflammation and the related mitochondrial impairment during PD progression may facilitate the development of promising therapies for PD. This review focuses on the molecular mechanisms underlying NLRP3 inflammasome activation, comprising priming and protein complex assembly, as well as the role of mitochondrial impairment and its subsequent inflammatory effects on the progression of neurodegeneration in PD. In addition, the therapeutic strategies targeting the NLRP3 inflammasome for PD treatment are discussed, including the inhibitors of NLRP3 inflammatory pathways, mitochondria-focused treatments, microRNAs, and other therapeutic compounds.
帕金森病（PD）是一种常见的神经退行性疾病，由黑质中多巴胺神经元的丧失和路易体的形成引起，路易体主要由α-突触核蛋白原纤维组成。α-突触核蛋白在核苷酸结合寡聚化结构域、富含亮氨酸重复序列和吡喃结构域包含蛋白 3（NLRP3）炎性小体介导的神经炎症中起着至关重要的作用。更好地了解 PD 进展过程中 NLRP3 炎性小体介导的神经炎症和相关的线粒体损伤，可能有助于开发有前途的 PD 治疗方法。本综述重点介绍 NLRP3 炎性小体激活的分子机制，包括引发和蛋白复合物组装，以及线粒体损伤及其随后对 PD 神经退行性变进展的炎症影响的作用。此外，还讨论了针对 PD 治疗的 NLRP3 炎性小体的治疗策略，包括 NLRP3 炎症途径的抑制剂、针对线粒体的治疗、microRNAs 和其他治疗化合物。
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