National Brain Research Centre, Manesar, Haryana-122051, India.
CNS Neurol Disord Drug Targets. 2013 Sep;12(6):726-40. doi: 10.2174/18715273113126660170.
Inflammation plays a critical role in the progression of neurodegenerative diseases. Microglia are the resident macrophages of the central nervous system (CNS) which actively take part in the neuronal development of CNS and are involved in clearance of pathogens as well as cellular debris from the system upon insult to this organization. Chronic activation of microglia in neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS) as well as inflammatory conditions of CNS such as multiple sclerosis (MS) results in overall upregulation of pro-inflammatory cytokines and chemokines in the brain parenchyma. This compromises the neuronal health which further activates microglia by releasing death associated molecules such as neuromelanin, Aβ peptides and cellular debris at the lesion site thereby forming a vicious cycle of disease advancement. Targeting microglial activation has proven to be a viable option in the treatment of inflammation related neurodegenerative diseases. This review will discuss the central position of inflammation and therapeutic strategies aiming to alleviate disease progression in some of the important inflammatory conditions of CNS.
炎症在神经退行性疾病的进展中起着关键作用。小胶质细胞是中枢神经系统 (CNS) 的常驻巨噬细胞,它们积极参与 CNS 的神经元发育,并在该组织受到损伤时参与清除病原体和细胞碎片。在神经退行性疾病(如阿尔茨海默病 (AD)、帕金森病 (PD)、亨廷顿病 (HD)、肌萎缩侧索硬化症 (ALS))和 CNS 的炎症状态(如多发性硬化症 (MS))中,小胶质细胞的慢性激活会导致大脑实质中促炎细胞因子和趋化因子的整体上调。这会损害神经元的健康,通过释放死亡相关分子(如神经元黑色素、Aβ 肽和细胞碎片)进一步激活小胶质细胞,从而在病变部位形成疾病进展的恶性循环。靶向小胶质细胞激活已被证明是治疗与炎症相关的神经退行性疾病的一种可行选择。这篇综述将讨论炎症的核心作用以及旨在减轻 CNS 一些重要炎症状态下疾病进展的治疗策略。