Campbell Arezoo
Department of Community and Environmental Medicine, University of California, 92697-1825, USA.
Ann N Y Acad Sci. 2004 Dec;1035:117-32. doi: 10.1196/annals.1332.008.
The etiology of neurodegenerative disorders is multifactorial and consists of an interaction between aging, environmental factors, and genetic predisposition. Neuronal cell loss in specific regions of the central nervous system and the resulting clinical symptoms are used to characterize different neurological syndromes. While the selectivity of neuronal cell death is not clearly understood, it is in part attributed to the physiological role and microenvironment of the impacted cells. In this review, innate immune responses in the central nervous system are described. Chronic upregulation of this pathway, orchestrated mainly by microglial cells, may jeopardize neuronal integrity through the prolonged production of toxic inflammatory mediators. Environmental exposures that further enhance the innate immune response may accelerate microglia-driven neurodegeneration. Environmental factors that can trigger inflammatory events in the central nervous system are lipopolysaccharide, aluminum, and particulate matter present in air pollution. These factors may enhance existing age-related inflammation in the central nervous system and thus accelerate neuronal toxicity.
神经退行性疾病的病因是多因素的,包括衰老、环境因素和遗传易感性之间的相互作用。中枢神经系统特定区域的神经元细胞丢失以及由此产生的临床症状用于表征不同的神经综合征。虽然神经元细胞死亡的选择性尚不清楚,但部分归因于受影响细胞的生理作用和微环境。在这篇综述中,描述了中枢神经系统中的先天免疫反应。这条通路的慢性上调主要由小胶质细胞精心调控,可能通过长期产生有毒的炎症介质危及神经元的完整性。进一步增强先天免疫反应的环境暴露可能加速小胶质细胞驱动的神经退行性变。可引发中枢神经系统炎症事件的环境因素包括空气污染中存在的脂多糖、铝和颗粒物。这些因素可能会增强中枢神经系统中现有的与年龄相关的炎症,从而加速神经元毒性。