Department of Neurology, Center for Translational Neuromedicine, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA.
Neurotherapeutics. 2010 Oct;7(4):413-23. doi: 10.1016/j.nurt.2010.07.001.
Astrocytes play direct, active, and critical roles in mediating neuronal survival and function in various neurodegenerative disorders. This role of astrocytes is well illustrated in amyotrophic lateral sclerosis (ALS), in which the removal of glutamate from the extracellular space by astrocytes confers neuroprotection, whereas astrocytic release of soluble toxic molecules promotes neurodegeneration. In recent years, this context-dependent dual role of astrocytes has also been documented in experimental models of Parkinson's disease. The present review addresses these studies and some potential mechanisms by which astrocytes may influence the neurodegenerative processes in Parkinson's disease, and in particular examines how astrocytes confer neuroprotection either through the removal of toxic molecules from the extracellular space or through the release of trophic factors and antioxidant molecules. In contrast, under pathological conditions, astrocytes release proinflammatory cytokines and other toxic molecules that are detrimental to dopaminergic neurons. These emerging roles of astrocytes in the pathogenesis of Parkinson's disease constitute an exciting development with promising novel therapeutic targets.
星形胶质细胞在介导各种神经退行性疾病中的神经元存活和功能中发挥直接、主动和关键作用。星形胶质细胞在肌萎缩侧索硬化症(ALS)中的这种作用得到了很好的说明,其中星形胶质细胞从细胞外空间去除谷氨酸赋予神经保护作用,而星形胶质细胞释放可溶性毒性分子则促进神经退行性变。近年来,在帕金森病的实验模型中也记录到了星形胶质细胞的这种上下文相关的双重作用。本综述讨论了这些研究以及星形胶质细胞可能影响帕金森病神经退行性过程的一些潜在机制,并特别研究了星形胶质细胞如何通过从细胞外空间去除毒性分子或通过释放营养因子和抗氧化分子来提供神经保护。相比之下,在病理条件下,星形胶质细胞释放促炎细胞因子和其他对多巴胺能神经元有害的毒性分子。星形胶质细胞在帕金森病发病机制中的这些新作用是一个令人兴奋的发展,具有有前途的新治疗靶点。