Yang Zhiyou, Liu Junxin, Wei Shuai, Deng Jiahang, Feng Xinyue, Liu Shucheng, Liu Mingxin
Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Guangdong Province Engineering Laboratory for Marine Biological Products, Guangdong Provincial Engineering Technology Research Center of Seafood, Key Laboratory of Advanced Processing of Aquatic Product of Guangdong Higher Education Institution, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang, China.
Collaborative Innovation Centre of Seafood Deep Processing, Dalian Polytechnic University, Dalian, China.
Front Pharmacol. 2023 Jan 9;13:1077222. doi: 10.3389/fphar.2022.1077222. eCollection 2022.
Alzheimer's disease (AD), the most common type of dementia, is an ageing-related progressive neurodegenerative brain disorder. Extracellular neuritic plaques composed of misfolded amyloid β (Aβ) proteins and intracellular neurofibrillary tangles formed by hyperphosphorylated tau protein are the two classical characteristics of AD. Aβ and tau pathologies induce neurite atrophy and neuronal apoptosis, leading to cognitive, language, and behavioral deficits. For decades, researchers have made great efforts to explore the pathogens and therapeutics of AD; however, its intrinsic mechanism remains unclear and there are still no well-established strategies to restore or even prevent this disease. Therefore, it would be beneficial for the establishment of novel therapeutic strategy to determine the intrinsic molecular mechanism that is interrelated with the initiation and progression of AD. A variety of evidence indicates that neuroinflammation plays a crucial role in the pathogenesis of AD. Nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain-containing protein 3 (NLRP3) is a key inflammasome sensor of cellular stress and infection that is involved in the innate immune system. In response to a wide range of stimuli like Aβ, NLRP3 assembles apoptosis-associated speck-like protein (ASC) and procaspase-1 into an inflammasome complex to induce the caspase-1 mediated secretion of interleukin (IL)-1β/IL-18 in M1 polarized microglia, triggering the pathophysiological changes and cognitive decline of AD. Therefore, targeting NLRP3 inflammasome seems an efficient path for AD treatment regulating brain immune microenvironment. Furthermore, accumulating evidence indicates that traditional Chinese medicine (TCM) exerts beneficial effects on AD NLRP3 inflammasome inactivation. In this review, we summarize current reports on the role and activated mechanisms of the NLRP3 inflammasome in the pathogenesis of AD. We also review the natural products for attenuating neuroinflammation by targeting NLRP3 inflammasome activation, which provides useful clues for developing novel AD treatments.
阿尔茨海默病（AD）是最常见的痴呆类型，是一种与衰老相关的进行性神经退行性脑疾病。由错误折叠的淀粉样β（Aβ）蛋白组成的细胞外神经炎性斑块和由过度磷酸化的tau蛋白形成的细胞内神经原纤维缠结是AD的两个经典特征。Aβ和tau病理学诱导神经突萎缩和神经元凋亡，导致认知、语言和行为缺陷。几十年来，研究人员一直在努力探索AD的病原体和治疗方法；然而，其内在机制仍不清楚，仍然没有成熟的策略来恢复甚至预防这种疾病。因此，确定与AD的发生和发展相关的内在分子机制将有助于建立新的治疗策略。各种证据表明，神经炎症在AD的发病机制中起关键作用。核苷酸结合寡聚化结构域（NOD）样受体含pyrin结构域蛋白3（NLRP3）是细胞应激和感染的关键炎性小体传感器，参与先天免疫系统。响应于多种刺激，如Aβ，NLRP3将凋亡相关斑点样蛋白（ASC）和前半胱天冬酶-1组装成炎性小体复合物，以诱导M1极化小胶质细胞中半胱天冬酶-1介导的白细胞介素（IL）-1β/IL-18分泌，引发AD的病理生理变化和认知衰退。因此，靶向NLRP3炎性小体似乎是调节脑免疫微环境治疗AD的有效途径。此外，越来越多的证据表明，中药对AD的NLRP3炎性小体失活具有有益作用。在这篇综述中，我们总结了目前关于NLRP3炎性小体在AD发病机制中的作用和激活机制的报道。我们还综述了通过靶向NLRP3炎性小体激活来减轻神经炎症的天然产物，这为开发新的AD治疗方法提供了有用的线索。
Zotero 插件