Parkinson's disease: Microglial/macrophage-induced immunoexcitotoxicity as a central mechanism of neurodegeneration.
Parkinson's disease: Microglial/macrophage-induced immunoexcitotoxicity as a central mechanism of neurodegeneration.
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DOI：
10.4103/sni.sni_441_16
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发表时间：
2017
影响因子：
--
通讯作者：
Blaylock RL
中科院分区：
文献类型：
--
作者：
Blaylock RL
帕金森氏病是影响老年人的几种神经退行性疾病之一，大约1%的60岁以上的人在一生中发展这种疾病。这种疾病在大多数人中具有进行性疾病的特征，在神经系统中发生的病理变化的共同模式超出了多巴胺能神经元的经典纹状体变性。早期的研究得出结论，这种疾病是一种α-突触核蛋白紊乱，其特征是形成异常α-突触核蛋白的聚集体。最近的研究得出结论，炎症在疾病中起着核心作用，并且特征性发现可以通过对α-突触核蛋白的突变或氧化损伤来解释，从而导致周围小胶质细胞，星形胶质细胞和巨噬细胞的免疫反应。在大多数这些研究中，几乎忽略了兴奋性毒性所起的作用，并且这两个过程密切相关，炎症触发的细胞信号传导增强了兴奋性毒性级联反应。此外，有越来越多的证据表明，这是兴奋性毒性反应，实际上导致神经变性。我创造了免疫兴奋性毒性这个名字来描述炎症和兴奋性毒性之间的联系。在神经退行性疾病中，这两个过程似乎很少（如果有的话）分开。
Parkinson's disease is one of the several neurodegenerative disorders that affects aging individuals, with approximately 1% of those over the age of 60 years developing the disorder in their lifetime. The disease has the characteristics of a progressive disorder in most people, with a common pattern of pathological change occurring in the nervous system that extends beyond the classical striatal degeneration of dopaminergic neurons. Earlier studies concluded that the disease was a disorder of alpha-synuclein, with the formation of aggregates of abnormal alpha-synuclein being characteristic. More recent studies have concluded that inflammation plays a central role in the disorder and that the characteristic findings can be accounted for by either mutation or oxidative damage to alpha-synuclein, with resulting immune reactions from surrounding microglia, astrocytes, and macrophages. What has been all but ignored in most of these studies is the role played by excitotoxicity and that the two processes are intimately linked, with inflammation triggered cell signaling enhancing the excitotoxic cascade. Further, there is growing evidence that it is the excitotoxic reactions that actually cause the neurodegeneration. I have coined the name immunoexcitotoxicity to describe this link between inflammation and excitotoxicity. It appears that the two processes are rarely, if ever, separated in neurodegenerative diseases.