Reynolds Ashley, Laurie Chad, Mosley R Lee, Gendelman Howard E
Department of Pharmacology and Experimental Neuroscience, Center for Neurovirology and Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA.
Int Rev Neurobiol. 2007;82:297-325. doi: 10.1016/S0074-7742(07)82016-2.
Microglia-derived inflammatory neurotoxins play a principal role in the pathogenesis of neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and HIV-associated dementia; chief among these is reactive oxygen species. The detrimental effects of oxidative stress in the brain and nervous system are primarily a result of the diminished capacity of the central nervous system to prevent ongoing oxidative damage. A spectrum of environmental cues, mitochondrial dysfunction, accumulation of aberrant misfolded proteins, inflammation, and defects in protein clearance are known to evolve and form as a result of disease progression. These factors likely affect glial function serving to accelerate the tempo of disease. Understanding the relationships between disease progression, free radical formation, neuroinflammation, and neurotoxicity is critical to elucidating disease mechanisms and the development of therapeutic modalities to combat disease processes. In an era where populations continue to age, the prevalence and incidence of age-related neurodegenerative diseases are on the rise; therefore, the need for novel therapeutic strategies that attenuate neuroinflammation and protect neurons against oxidative stress is ever more immediate.
小胶质细胞衍生的炎性神经毒素在包括阿尔茨海默病、帕金森病、肌萎缩侧索硬化症和人类免疫缺陷病毒相关痴呆症在内的神经退行性疾病的发病机制中起主要作用；其中主要的是活性氧。氧化应激对大脑和神经系统的有害影响主要是由于中枢神经系统预防持续性氧化损伤的能力下降所致。已知一系列环境线索、线粒体功能障碍、异常错误折叠蛋白的积累、炎症以及蛋白质清除缺陷会随着疾病进展而演变并形成。这些因素可能影响神经胶质细胞功能，从而加速疾病进程。了解疾病进展、自由基形成、神经炎症和神经毒性之间的关系对于阐明疾病机制以及开发对抗疾病进程的治疗方法至关重要。在人口持续老龄化的时代，与年龄相关的神经退行性疾病的患病率和发病率正在上升；因此，迫切需要新的治疗策略来减轻神经炎症并保护神经元免受氧化应激的影响。
