NLRP3 炎性小体/细胞焦亡激活的机制及其在帕金森病中的作用。
The mechanisms of NLRP3 inflammasome/pyroptosis activation and their role in Parkinson's disease.
机构信息
State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
出版信息
Int Immunopharmacol. 2019 Feb;67:458-464. doi: 10.1016/j.intimp.2018.12.019. Epub 2018 Dec 27.
Parkinson's disease (PD) is a typical neurodegenerative disease and the pathological feature of which is the death of dopamine neurons in the substantia nigra region. At present, neuronal death caused by inflammatory cytokine-mediated neuroinflammation is being extensively studied. The nucleotide-binding oligomerization domain-, leucine-rich repeat and pyrin domain-containing 3 (NLRP3) inflammasome is an inflammatory complex existing in microglia. Its activation promotes the secretion of the inflammatory cytokine interleukin-1β/18 (IL-1β/18) and induces pyroptosis, a type of cell death that possesses the potential for inflammation, to rupture microglia to further release IL-1β. In this review we focus on the mechanisms of activation of the NLRP3 inflammasome and pyroptosis and their inflammatory effects on the development of PD. In addition, we focus on some inhibitors of NLRP3 inflammatory pathways to alleviate the progression of PD by inhibiting central inflammation and provide new therapeutic strategies for the treatment of PD.
帕金森病(PD)是一种典型的神经退行性疾病,其病理特征是黑质区域多巴胺神经元的死亡。目前,炎症细胞因子介导的神经炎症导致的神经元死亡正在被广泛研究。核苷酸结合寡聚化结构域、富含亮氨酸重复序列和pyrin 结构域蛋白 3(NLRP3)炎性小体是一种存在于小胶质细胞中的炎症复合物。其激活可促进炎性细胞因子白细胞介素-1β/18(IL-1β/18)的分泌,并诱导具有炎症潜能的细胞死亡形式——细胞焦亡,使小胶质细胞破裂,进一步释放 IL-1β。本综述重点介绍 NLRP3 炎性小体和细胞焦亡的激活机制及其对 PD 发展的炎症作用。此外,我们还关注了一些 NLRP3 炎症途径的抑制剂,通过抑制中枢炎症来缓解 PD 的进展,为 PD 的治疗提供新的治疗策略。