Department of Pathology, The University of Melbourne, Victoria 3010, Australia.
Cell and Molecular Biology, QIMR Berghofer Medical Research Institute, Herston, Queensland 4006, Australia.
Neurochem Int. 2018 Jul;117:126-138. doi: 10.1016/j.neuint.2017.05.016. Epub 2017 May 31.
Parkinson's disease is neuropathologically characterised by loss of catecholamine neurons in vulnerable brain regions including substantia nigra pars compacta and locus coeruleus. This review discusses how the susceptibility of these regions is defined by their shared biochemical characteristics that differentiate them from other neurons. Parkinson's disease is biochemically characterised by mitochondrial dysfunction, accumulation of iron, diminished copper content and depleted glutathione levels in these regions. This review also discusses this neuropathology, and provides evidence for how these pathological features are mechanistically linked to each other. This leads to the conclusion that disruption of mitochondrial function, or iron, copper or glutathione metabolism in isolation provokes the pathological impairment of them all. This creates a vicious cycle that drives pathology leading to mitochondrial failure and neuronal cell death in vulnerable brain regions.
帕金森病在神经病理学上的特征是包括黑质致密部和蓝斑在内的易损脑区儿茶酚胺神经元的丧失。本综述讨论了这些区域的易感性如何通过其与其他神经元区分开来的共同生化特征来定义。帕金森病在生化上的特征是这些区域的线粒体功能障碍、铁的积累、铜含量降低和谷胱甘肽水平降低。本综述还讨论了这种神经病理学，并提供了证据表明这些病理特征是如何在机制上相互关联的。这就得出结论，即线粒体功能、铁、铜或谷胱甘肽代谢的中断单独引起所有这些病理损伤。这就形成了一个恶性循环，导致易损脑区的线粒体功能衰竭和神经元细胞死亡。
