Chronic microglial activation and progressive dopaminergic neurotoxicity
Chronic microglial activation and progressive dopaminergic neurotoxicity
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DOI：
10.1042/bst0351127
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发表时间：
2007-11-01
影响因子：
3.9
通讯作者：
Hong, J. -S.
中科院分区：
文献类型：
--
作者：
Block, M. L.;Hong, J. -S.
PD（帕金森病）的特征是黑质中DA神经元（多巴胺能神经元）的选择性和进行性丧失。炎症和小胶质细胞（大脑中固有的免疫细胞）的激活与神经退行性疾病（如帕金森病）密切相关。小胶质细胞可以对免疫刺激和神经元死亡作出反应，产生大量的毒性因子，包括细胞因子和活性氧。小胶质细胞也可以在单一刺激后持续激活，并在刺激消失后很长一段时间内保持细胞因子和活性氧的升高。目前的报道表明，这种慢性小胶质细胞激活可能是由死亡/受损的神经元或来自局部胶质细胞（如细胞因子）的自分泌和旁分泌信号引起的。在这里，我们回顾了慢性神经炎症的机制，并解释了有害的小胶质细胞激活、DA神经元损伤和神经退行性疾病之间的相互关系。
PD (Parkinson's disease) is characterized by the selective and progressive loss of DA neurons (dopaminergic neurons) in the substantia nigra. inflammation and activation of microglia, the resident innate immune cell in the brain, have been strongly linked to neurodegenerative diseases, such as PD. Microglia can respond to immunological stimuli and neuronal death to produce a host of toxic factors, including cytokines and ROS (reactive oxygen species). Microglia can also become persistently activated after a single stimulus and maintain the elevated production of both cytokines and ROS, long after the instigating stimulus is gone. current reports suggest that this chronic microglial activation may be fuelled by either dying/damaged neurons or autocrine and paracrine signals from local glial cells, such as cytokines. Here, we review proposed mechanisms responsible for chronic neuroinflammation and explain the interconnected relationship between deleterious microglial activation, DA neuron damage and neurodegenerative disease.