Alzheimer’s disease (AD) is a common neurodegenerative disease of progressive dementia which is characterized pathologically by extracellular neuritic plaques containing aggregated amyloid beta (Aβ) and intracellular hyperphosphorylated tau protein tangles in cerebrum. It has been confirmed that microglia-specific nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome-mediated chronic neuroinflammation plays a crucial role in the pathogenesis of AD. Stimulated by Aβ deposition, NLRP3 assembles and activates within microglia in the AD brain, leading to caspase-1 activation along with downstream interleukin (IL)-1β secretion, and subsequent inflammatory events. Activation of the NLRP3 inflammasome mediates microglia to exhibit inflammatory M1 phenotype, with high expression of caspase-1 and IL-1β. This leads to Aβ deposition and neuronal loss in the amyloid precursor protein (APP)/human presenilin-1 (PS1) mouse model of AD. However, NLRP3 or caspase-1 deletion in APP/PS1 mice promotes microglia to transform to an anti-inflammatory M2 phenotype, with decreased secretion of caspase-1 and IL-1β. It also results in improved cognition, enhanced Aβ clearance, and a lower cerebral inflammatory response. This result suggests that the NLRP3 inflammasome may be an appropriate target for reducing neuroinflammation and alleviating pathological processes in AD. In the present review, we summarize the generally accepted regulatory mechanisms of NLRP3 inflammasome activation, and explore its role in neuroinflammation. Furthermore, we speculate on the possible roles of microglia-specific NLRP3 activation in AD pathogenesis and consider potential therapeutic interventions targeting the NLRP3 inflammasome in AD.

阿尔茨海默病 (Alzheimer's disease, AD) 是一种常见的进行性痴呆的神经退行性疾病，其病理特征是细胞外神经炎斑块含有聚集的β淀粉样蛋白 (Aβ) 和细胞内过度磷酸化的 tau 蛋白缠结在大脑中。已经证实，小胶质细胞特异性核苷酸结合寡聚化结构域 (NOD) 样受体蛋白 3 (NLRP3) 炎症小体介导的慢性神经炎症在 AD 的发病机制中起关键作用。在 Aβ 沉积的刺激下，NLRP3 在 AD 大脑的小胶质细胞内组装和激活，导致 caspase-1 激活以及下游白细胞介素 (IL)-1β 分泌和随后的炎症事件。NLRP3 炎性体的激活介导小胶质细胞表现出炎性 M1 表型，高表达 caspase-1 和 IL-1β。这导致 AD 的淀粉样前体蛋白 (APP)/人早老素-1 (PS1) 小鼠模型中的 Aβ 沉积和神经元丢失。然而，APP/PS1 小鼠中的 NLRP3 或 caspase-1 缺失促进小胶质细胞转化为抗炎 M2 表型，同时 caspase-1 和 IL-1β 的分泌减少。它还可以改善认知、增强 Aβ 清除率和降低脑炎症反应。该结果表明 NLRP3 炎性体可能是减少神经炎症和缓解 AD 病理过程的合适靶标。在本综述中，我们总结了公认的 NLRP3 炎症小体激活的调节机制，并探讨其在神经炎症中的作用。此外，