Interaction between autophagy and the NLRP3 inflammasome in Alzheimer's and Parkinson's disease.
Interaction between autophagy and the NLRP3 inflammasome in Alzheimer's and Parkinson's disease.
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DOI：
10.3389/fnagi.2022.1018848
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发表时间：
2022
影响因子：
4.8
通讯作者：
中科院分区：
文献类型：
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自噬通过溶酶体降解吞噬受损的细胞器、错误折叠的蛋白质和各种病原体，作为维持细胞稳态的重要方式。自噬是一种严格调控的细胞自我降解过程，在维持正常细胞功能和体内稳态方面发挥着至关重要的作用。神经炎症中的NLRP3炎症小体是先天细胞免疫中重要的识别受体，感知外部入侵的病原体和内源性刺激，并进一步引发炎症反应。 NLRP3炎症小体通过识别DAMPS或PAMPS形成炎症复合物，其激活触发caspase-1介导的pro-IL-1β和pro-IL-18裂解，促进炎症反应。近年来，有报道称自噬与神经炎症之间存在复杂的相互作用。加强自噬可以调节NLRP3炎症小体的表达，从而减少神经退行性疾病中的神经炎症，保护神经元。但相关机制尚不完全清楚。蛋白质聚集体的形成是神经退行性疾病的标准特征之一。大量有毒蛋白质聚集体可诱发炎症。理论上，自噬途径的激活可以消除蛋白质聚集体的潜在毒性并延缓疾病的进展。本文旨在综述近年来自噬、NLRP3炎症小体和蛋白质聚集体在阿尔茨海默病（AD）和帕金森病（PD）中相互作用的研究进展，分析其机制，为今后的进一步研究提供理论参考。
Autophagy degrades phagocytosed damaged organelles, misfolded proteins, and various pathogens through lysosomes as an essential way to maintain cellular homeostasis. Autophagy is a tightly regulated cellular self-degradation process that plays a crucial role in maintaining normal cellular function and homeostasis in the body. The NLRP3 inflammasome in neuroinflammation is a vital recognition receptor in innate cellular immunity, sensing external invading pathogens and endogenous stimuli and further triggering inflammatory responses. The NLRP3 inflammasome forms an inflammatory complex by recognizing DAMPS or PAMPS, and its activation triggers caspase-1-mediated cleavage of pro-IL-1β and pro-IL-18 to promote the inflammatory response. In recent years, it has been reported that there is a complex interaction between autophagy and neuroinflammation. Strengthening autophagy can regulate the expression of NLRP3 inflammasome to reduce neuroinflammation in neurodegenerative disease and protect neurons. However, the related mechanism is not entirely clear. The formation of protein aggregates is one of the standard features of Neurodegenerative diseases. A large number of toxic protein aggregates can induce inflammation. In theory, activation of the autophagy pathway can remove the potential toxicity of protein aggregates and delay the progression of the disease. This article aims to review recent research on the interaction of autophagy, NLRP3 inflammasome, and protein aggregates in Alzheimer’s disease (AD) and Parkinson’s disease (PD), analyze the mechanism and provide theoretical references for further research in the future.