Biswas Kaushiki
Department of Life Sciences, Presidency University Main campus, 86/1 College Street, Kolkata 700073, India.
J Neuroimmunol. 2023 Oct 15;383:578180. doi: 10.1016/j.jneuroim.2023.578180. Epub 2023 Aug 26.
Microglia, the immune sentinels of the central nervous system (CNS), have emerged to be the central players in many neurological and neurodegenerative diseases. Recent studies on large genome databases and omics studies in fact provide support to the idea that microglial cells could be the drivers of these diseases. Microglial cells have the capacity to undergo morphological and phenotypic transformations depending on its microenvironment. From the homeostatic ramified state, they can shift their phenotypes between the two extremes, known as the proinflammatory M1 and anti-inflammatory M2 phenotype, with intermediate transitional states, characterized by different transcriptional signature and release of inflammatory mediators. The temporal regulation of the release of the inflammatory factors are critical for damage control and steering the microglia back towards homeostatic conditions. A dysregulation in these can lead to excessive tissue damage and neuronal death. Therefore, targeting the cell signaling pathways that are the underpinnings of microglial modulations are considered to be an important avenue for treatment of various neurodegenerative diseases. In this review we have discussed various signaling pathways that trigger microglial activation from its ramified state and highlight the mechanisms of microglia-mediated neuroinflammation that are associated with various neurodegenerative diseases. Most of the cellular factors that drive microglia towards a proinflammatory phenotype are components of the immune system signaling pathways and cell proliferation, along with certain ion channels. The anti-inflammatory phenotype is mainly elicited by purinoceptors, metabolic receptors and other receptors that primarily suppress the production proinflammatory mediators.
小胶质细胞作为中枢神经系统（CNS）的免疫哨兵，已成为许多神经和神经退行性疾病的核心参与者。近期对大型基因组数据库的研究和组学研究实际上为小胶质细胞可能是这些疾病的驱动因素这一观点提供了支持。小胶质细胞能够根据其微环境进行形态和表型的转变。从稳态的分支状态，它们可以在两种极端表型之间转换，即促炎的M1型和抗炎的M2型，中间还有过渡状态，其特征是不同的转录特征和炎症介质的释放。炎症因子释放的时间调节对于控制损伤和引导小胶质细胞恢复稳态至关重要。这些调节的失调会导致过度的组织损伤和神经元死亡。因此，靶向作为小胶质细胞调节基础的细胞信号通路被认为是治疗各种神经退行性疾病的重要途径。在这篇综述中，我们讨论了从其分支状态触发小胶质细胞激活的各种信号通路，并强调了与各种神经退行性疾病相关的小胶质细胞介导的神经炎症机制。大多数促使小胶质细胞向促炎表型转变的细胞因子是免疫系统信号通路和细胞增殖的组成部分，以及某些离子通道。抗炎表型主要由嘌呤受体、代谢受体和其他主要抑制促炎介质产生的受体引发。
