Tantra Tanmoy, Rahaman T A Abdul, Chaudhary Sandeep
Laboratory of Bioactive Heterocycles and Catalysis (BHC Lab), Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research-Raebareli (Transit Campus), Bijnor-Sisendi Road, Near CRPF Base Camp, Sarojini Nagar, Lucknow 226002, India.
Laboratory of Bioactive Heterocycles and Catalysis (BHC Lab), Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research-Raebareli (Transit Campus), Bijnor-Sisendi Road, Near CRPF Base Camp, Sarojini Nagar, Lucknow 226002, India.
Bioorg Chem. 2024 Dec;153:107912. doi: 10.1016/j.bioorg.2024.107912. Epub 2024 Oct 23.
The NLRP3 inflammasome is a multiprotein complex that plays a vital role in regulating inflammatory signaling and the innate immune system. Activation of NLRP3 by accumulation of Aβ leads to its oligomerization and the activation of caspase-1, resulting in the secretion of pro-cytokines such as IL-18 and IL-1β. These pro-cytokines can contribute to cognitive impairment and neurodegeneration. The activation of NLRP3 is associated with neuroinflammation in animal models of Alzheimer's disease (AD). Therefore, the NLRP3 inflammasome is considered a potential therapeutic target for AD. Various natural and synthetic molecules have gained attention as NLRP3 inhibitors against AD. In this review, we will summarize the sources, chemical structures, synthesis, and biological activity of NLRP3 inhibitors as anti-Alzheimer's agents. Additionally, we will critically analyze the structure-activity relationship (SAR) of NLRP3 inhibitors. This detailed examination of the SAR-based investigation of NLRP3 inhibitors and their derivatives offers insights into the design and development of novel NLRP3 inhibitors as anti-Alzheimer's agents. It is expected that this review will assist researchers in developing innovative and effective NLRP3 inhibitors for the treatment of AD.
NLRP3炎性小体是一种多蛋白复合体，在调节炎症信号传导和先天免疫系统中发挥着至关重要的作用。β-淀粉样蛋白（Aβ）的积累激活NLRP3，导致其寡聚化并激活半胱天冬酶-1，从而导致白细胞介素-18（IL-18）和白细胞介素-1β（IL-1β）等前细胞因子的分泌。这些前细胞因子可导致认知障碍和神经退行性变。在阿尔茨海默病（AD）动物模型中，NLRP3的激活与神经炎症有关。因此，NLRP3炎性小体被认为是AD的一个潜在治疗靶点。各种天然和合成分子作为抗AD的NLRP3抑制剂受到关注。在这篇综述中，我们将总结作为抗阿尔茨海默病药物的NLRP3抑制剂的来源、化学结构、合成方法和生物活性。此外，我们将批判性地分析NLRP3抑制剂的构效关系（SAR）。对基于SAR的NLRP3抑制剂及其衍生物的研究进行的详细考察，为新型抗阿尔茨海默病NLRP3抑制剂的设计和开发提供了见解。预计这篇综述将有助于研究人员开发创新且有效的NLRP3抑制剂来治疗AD。
