Department of Sciences and Technologies for Humans and Environment, Università Campus Bio-Medico di Roma, Via Álvaro del Portillo, 21, 00128 Rome, Italy.
Department of Sciences and Technologies for Humans and Environment, Università Campus Bio-Medico di Roma, Via Álvaro del Portillo, 21, 00128 Rome, Italy; Department of Experimental Neurosciences, IRCCS Santa Lucia Foundation, Via del Fosso di Fiorano, 64, 00143 Rome, Italy.
Ageing Res Rev. 2023 Jun;87:101907. doi: 10.1016/j.arr.2023.101907. Epub 2023 Mar 8.
In the Central Nervous System (CNS), neuroinflammation orchestrated by microglia and astrocytes is an innate immune response to counteract stressful and dangerous insults. One of the most important and best characterized players in the neuroinflammatory response is the NLRP3 inflammasome, a multiproteic complex composed by NOD-like receptor family Pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein (ASC) and pro-caspase-1. Different stimuli mediate NLRP3 activation, resulting in the NLRP3 inflammasome assembly and the pro-inflammatory cytokine (IL-1β and IL-18) maturation and secretion. The persistent and uncontrolled NLRP3 inflammasome activation has a leading role during the pathophysiology of neuroinflammation in age-related neurodegenerative diseases such as Parkinson's (PD) and Alzheimer's (AD). The neurotransmitter dopamine (DA) is one of the players that negatively modulate NLRP3 inflammasome activation through DA receptors expressed in both microglia and astrocytes. This review summarizes recent findings linking the role of DA in the modulation of NLRP3-mediated neuroinflammation in PD and AD, where early deficits of the dopaminergic system are well characterized. Highlighting the relationship between DA, its glial receptors and the NLRP3-mediated neuroinflammation can provide insights to novel diagnostic strategies in early disease phases and new pharmacological tools to delay the progression of these diseases.
在中枢神经系统 (CNS) 中，由小胶质细胞和星形胶质细胞协调的神经炎症是一种固有免疫反应，以对抗应激和危险的损伤。神经炎症反应中最重要和研究最充分的一个重要角色是 NLRP3 炎性体，它是一种由 NOD 样受体家族富含 Pyrin 域蛋白 3 (NLRP3)、凋亡相关斑点样蛋白 (ASC) 和前胱天蛋白酶-1 组成的多蛋白复合物。不同的刺激介导 NLRP3 的激活，导致 NLRP3 炎性体的组装以及促炎细胞因子（IL-1β 和 IL-18）的成熟和分泌。在与年龄相关的神经退行性疾病（如帕金森病 (PD) 和阿尔茨海默病 (AD)）的神经炎症病理生理学中，持续和不受控制的 NLRP3 炎性体激活起着主导作用。神经递质多巴胺 (DA) 是通过小胶质细胞和星形胶质细胞中表达的 DA 受体负调控 NLRP3 炎性体激活的众多参与者之一。本综述总结了最近的发现，这些发现将 DA 在 PD 和 AD 中调节 NLRP3 介导的神经炎症中的作用联系起来，其中多巴胺能系统的早期缺陷得到了很好的描述。强调 DA、其神经胶质受体与 NLRP3 介导的神经炎症之间的关系，可以为早期疾病阶段提供新的诊断策略，并为延缓这些疾病的进展提供新的药理学工具。
