The Role of NLRP3 Inflammasome in Alzheimer's Disease and Potential Therapeutic Targets.
The Role of NLRP3 Inflammasome in Alzheimer's Disease and Potential Therapeutic Targets.
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NLRP3 炎症小体在阿尔茨海默病中的作用和潜在的治疗靶点
DOI：
10.3389/fphar.2022.845185
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发表时间：
2022
影响因子：
5.6
通讯作者：
Wang L
中科院分区：
文献类型：
--
作者：
Liang T;Zhang Y;Wu S;Chen Q;Wang L
阿尔茨海默病(AD)是一种常见的与年龄相关的神经退行性疾病，以进行性认知功能障碍和行为障碍为特征。AD的典型病理特征是由淀粉样蛋白(Aβ)组成的细胞外老年斑、微管相关蛋白tau过度磷酸化形成的细胞内神经原纤维缠结和神经元丢失。在过去的一百年里，尽管人类投入了大量的人力、物力和财力，但到目前为止，世界上还没有一种被广泛认可的有效预防和临床治疗阿尔茨海默病的药物。因此，评估和探索治疗AD的新药靶点是一个重要的课题。目前，研究人员对阿尔茨海默病发病机制的探索并未停止，对阿尔茨海默病发病因素的看法也在不断变化。大量证据证实，慢性神经炎在AD的发病机制中起着至关重要的作用。在神经炎症领域，核苷酸结合的寡聚化结构域样受体3(NLRP3)炎症体是AD神经炎性通路中的关键分子环节。在Aβ寡聚体和tau聚合体的刺激下，可导致脑内小胶质细胞和星形胶质细胞中NLRP3炎性小体的组装和激活，从而引起Caspase-1的激活和IL-1β和IL-18的分泌，最终触发AD的病理生理变化和认知功能下降。本文就NLRP3炎症体的激活及其相关调控机制的研究进展进行综述，并探讨其在AD发病机制中的可能作用。此外，以NLRP3炎症体为研究对象，结合NLRP3炎症体的上下游信号通路相关分子为靶点，综述了通过调节NLRP3炎症体的激活来减轻神经炎症的药理相关靶点和各种方法，为AD的治疗提供了新的思路。
Alzheimer’s disease (AD) is a common age-related neurodegenerative disease characterized by progressive cognitive dysfunction and behavioral impairment. The typical pathological characteristics of AD are extracellular senile plaques composed of amyloid ß (Aβ) protein, intracellular neurofibrillary tangles formed by the hyperphosphorylation of the microtubule-associated protein tau, and neuron loss. In the past hundred years, although human beings have invested a lot of manpower, material and financial resources, there is no widely recognized drug for the effective prevention and clinical cure of AD in the world so far. Therefore, evaluating and exploring new drug targets for AD treatment is an important topic. At present, researchers have not stopped exploring the pathogenesis of AD, and the views on the pathogenic factors of AD are constantly changing. Multiple evidence have confirmed that chronic neuroinflammation plays a crucial role in the pathogenesis of AD. In the field of neuroinflammation, the nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 3 (NLRP3) inflammasome is a key molecular link in the AD neuroinflammatory pathway. Under the stimulation of Aβ oligomers and tau aggregates, it can lead to the assembly and activation of NLRP3 inflammasome in microglia and astrocytes in the brain, thereby causing caspase-1 activation and the secretion of IL-1β and IL-18, which ultimately triggers the pathophysiological changes and cognitive decline of AD. In this review, we summarize current literatures on the activation of NLRP3 inflammasome and activation-related regulation mechanisms, and discuss its possible roles in the pathogenesis of AD. Moreover, focusing on the NLRP3 inflammasome and combining with the upstream and downstream signaling pathway-related molecules of NLRP3 inflammasome as targets, we review the pharmacologically related targets and various methods to alleviate neuroinflammation by regulating the activation of NLRP3 inflammasome, which provides new ideas for the treatment of AD.
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影响因子：
16.6
作者：
Daniels MJ;Rivers-Auty J;Schilling T;Spencer NG;Watremez W;Fasolino V;Booth SJ;White CS;Baldwin AG;Freeman S;Wong R;Latta C;Yu S;Jackson J;Fischer N;Koziel V;Pillot T;Bagnall J;Allan SM;Paszek P;Galea J;Harte MK;Eder C;Lawrence CB;Brough D
通讯作者：
Brough D
影响因子：
3.7
作者：
Cha MY;Han SH;Son SM;Hong HS;Choi YJ;Byun J;Mook-Jung I
通讯作者：
Mook-Jung I
影响因子：
5.9
作者：
Byeon HE;Jeon JY;Kim HJ;Kim DJ;Lee KW;Kang Y;Han SJ
通讯作者：
Han SJ
影响因子：
13.3
作者：
Cho, Mi-Hyang;Cho, Kwangmin;Yoon, Seung-Yong
通讯作者：
Yoon, Seung-Yong
影响因子：
5.6
作者：
Ali M;Gupta M;Wani A;Sharma A;Abdullaha M;Kour D;Choudhary S;Bharate SB;Singh G;Kumar A
通讯作者：
Kumar A