Foley P, Riederer P
Clinical Neurochemistry, Department of Psychiatry, University of Würzburg, Germany.
J Neurol. 2000 Apr;247 Suppl 2:II82-94. doi: 10.1007/pl00007766.
It is generally accepted that progressive, irreversible and regionally specific neurodegeneration and the presence of Lewy bodies are the essential pathological hallmarks of idiopathic parkinsonism. The causes of these phenomena, however, remain to be elucidated. One of the leading hypotheses is that oxidative stress induced by reactive oxygen species (ROS), such as the hydroxyl radical, damages essential components of the neuron, resulting ultimately in cell death. Observations in the parkinsonian brain at post-mortem support this hypothesis; for example, widespread oxidative protein modification is evident. There are several potential sources of increased oxidative stress in Parkinson's disease, including mitochondrial dysfunction, increased free iron levels and impaired free radical defence mechanisms. Further, it is possible that glial, rather than neuronal, elements are primarily responsible for the initial increase in oxidative stress in the substantia nigra. It is likely that parkinsonism is the result of aberrations at multiple levels of neuronal function. Oxidative stress is no doubt one of the events involved in neurodegeneration, but is unlikely to be the initiating event. It is to be expected that the search for this event will continue for many years.
一般认为，进行性、不可逆且具有区域特异性的神经退行性变以及路易小体的存在是特发性帕金森病的基本病理特征。然而，这些现象的原因仍有待阐明。其中一个主要假说是，诸如羟基自由基等活性氧（ROS）诱导的氧化应激会损害神经元的重要组成部分，最终导致细胞死亡。帕金森病患者死后大脑的观察结果支持这一假说；例如，广泛的氧化蛋白修饰很明显。帕金森病中氧化应激增加有几个潜在来源，包括线粒体功能障碍、游离铁水平升高和自由基防御机制受损。此外，有可能胶质细胞而非神经元成分是黑质中氧化应激最初增加的主要原因。帕金森病很可能是神经元功能多个层面异常的结果。氧化应激无疑是神经退行性变所涉及的事件之一，但不太可能是起始事件。预计对这一事件的探索还将持续多年。
