Department of Pharmacology, Monash University, Clayton, Alfred Medical Research and Education Precinct, Melbourne, Victoria, Australia.
Clin Exp Pharmacol Physiol. 2013 Aug;40(8):571-9. doi: 10.1111/1440-1681.12099.
Microglia are the resident immune cells within the brain and retina, commonly known as the macrophages of the central nervous system (CNS). Microglia survey the surrounding milieu to eliminate invading microbes, clear cellular debris and enforce programmed cell death by removing apoptotic cells. Complementary to their 'house-keeping' role, microglia are capable of releasing brain-derived neurotrophic factor (BDNF), as well as various anti-inflammatory cytokines that sustain and support neuronal survival. Although microglia are essential for maintaining a healthy CNS, paradoxically they may undergo phenotypic changes to influence numerous neurodegenerative disorders, including Parkinson's disease and Alzheimer's disease. Understanding the underlying mechanisms that determine whether microglia are supportive or toxic could elucidate novel and more effective therapeutic targets to treat an array of neurological and retinal diseases. Although relatively little is known about the influences that evoke phenotypic changes in the microglial population, there is accumulating evidence illustrating an interaction with the renin-angiotensin system (RAS). The angiotensin AT1 and AT2 receptors may have differential roles in mediating the activity of microglia. Understanding the actions of these angiotensin receptors will be important in defining whether microglia are an important therapeutic target for RAS blockade in brain and ocular diseases.
小胶质细胞是大脑和视网膜中的常驻免疫细胞，通常被称为中枢神经系统 (CNS) 的巨噬细胞。小胶质细胞监测周围环境，以消除入侵的微生物，清除细胞碎片，并通过清除凋亡细胞来执行程序性细胞死亡。除了它们的“管家”作用外，小胶质细胞还能够释放脑源性神经营养因子 (BDNF) 以及各种抗炎细胞因子，以维持和支持神经元的存活。尽管小胶质细胞对于维持健康的 CNS 至关重要，但它们可能会发生表型变化，从而影响多种神经退行性疾病，包括帕金森病和阿尔茨海默病。了解决定小胶质细胞是支持还是有毒的潜在机制，可以阐明治疗一系列神经和视网膜疾病的新的、更有效的治疗靶点。尽管对于引起小胶质细胞群体表型变化的影响知之甚少，但越来越多的证据表明存在与肾素-血管紧张素系统 (RAS) 的相互作用。血管紧张素 AT1 和 AT2 受体在介导小胶质细胞活性方面可能具有不同的作用。了解这些血管紧张素受体的作用对于确定 RAS 阻断是否是大脑和眼部疾病中小胶质细胞的重要治疗靶点将非常重要。
