Laboratório Neurofarmacologia, Departamento de Farmacologia, ICB-UFMG, Belo Horizonte MG, 31270 - 901, Brazil.
COLTEC-UFMG, Belo Horizonte MG, 31270 - 901, Brazil.
Curr Neuropharmacol. 2023;21(2):202-212. doi: 10.2174/1570159X20666220327215245.
Alzheimer's disease (AD), the most prevalent form of dementia, is a complex clinical condition with multifactorial origin posing a major burden to health care systems across the world. Even though the pathophysiological mechanisms underlying the disease are still unclear, both central and peripheral inflammation has been implicated in the process. Piling evidence shows that the nucleotide-binding domain, leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3) inflammasome is activated in AD. As dyslipidemia is a risk factor for dementia, and cholesterol can also activate the inflammasome, a possible link between lipid levels and the NLRP3 inflammasome has been proposed in Alzheimer's. It is also speculated that not only cholesterol but also its metabolites, the oxysterols, may be involved in AD pathology. In this context, mounting data suggest that NLRP3 inflammasome activity can be modulated by different peripheral nuclear receptors, including liver-X receptors, which present oxysterols as endogenous ligands. In light of this, the current review explores whether the activation of NLRP3 by nuclear receptors, mediated by oxysterols, may also be involved in AD and could serve as a potential pharmacological avenue in dementia.
阿尔茨海默病（AD）是最常见的痴呆症形式，是一种具有多因素起源的复杂临床病症，给全球的医疗保健系统带来了重大负担。尽管该疾病的病理生理学机制尚不清楚，但中枢和外周炎症都与该疾病的发生有关。越来越多的证据表明，核苷酸结合域、富含亮氨酸重复和吡喃结构域蛋白 3（NLRP3）炎性小体在 AD 中被激活。由于血脂异常是痴呆的一个危险因素，胆固醇也可以激活炎性小体，因此有人提出脂质水平与 NLRP3 炎性小体之间可能存在联系。此外，还有推测认为，参与 AD 病理的不仅是胆固醇，还有其代谢产物——氧化固醇。在这种情况下，越来越多的数据表明，NLRP3 炎性小体的活性可以通过不同的外周核受体来调节，包括肝 X 受体，其将氧化固醇作为内源性配体。鉴于此，目前的综述探讨了核受体通过氧化固醇激活 NLRP3 是否也与 AD 有关，并且是否可以作为痴呆症的潜在药物治疗途径。
