Good P F, Hsu A, Werner P, Perl D P, Olanow C W
Department of Pathology and the Fishberg Research Center for Neurobiology, The Mount Sinai School of Medicine, New York City, New York 10029-6574, USA.
J Neuropathol Exp Neurol. 1998 Apr;57(4):338-42. doi: 10.1097/00005072-199804000-00006.
Oxidative stress has been proposed as a pathogenetic mechanism in Parkinson's disease (PD). One mechanism of oxidative cellular injury is the nitration of protein tyrosine residues, mediated by peroxynitrite, a reaction product of nitric oxide and superoxide radicals. We demonstrate here the presence of nitrotyrosine immunoreactivity in Lewy bodies within melanized neurons and in amorphous deposits associated with intact and degenerating neurons. The core of the Lewy body was frequently intensely immunolabeled, while the rim was lightly labeled or unlabeled. This likely reflects the fact that tyrosine residues of neurofilament proteins are primarily localized to Lewy body cores, and suggests that nitrotyrosine is present in neurofilament protein itself. Although these observations are as yet unable to provide a definitive link between oxidative stress and neuronal dysfunction, they demonstrate that oxidative stress has occurred within the vulnerable neurons of PD, leaving a permanent marker of oxidative modification of neuronal proteins within the target cells of neurodegeneration. In addition, these observations provide a potential link between excitotoxicity and oxidative stress within the vulnerable neurons of PD and represent a pathogenetic mechanism in common with the 2 other major age-related neurodegenerative diseases, Alzheimer disease and amyotrophic lateral sclerosis.
氧化应激被认为是帕金森病（PD）的一种发病机制。细胞氧化损伤的一种机制是蛋白质酪氨酸残基的硝化作用，由过氧亚硝酸盐介导，过氧亚硝酸盐是一氧化氮和超氧自由基的反应产物。我们在此证明，在黑素化神经元内的路易小体以及与完整和变性神经元相关的无定形沉积物中存在硝基酪氨酸免疫反应性。路易小体的核心通常有强烈的免疫标记，而边缘则标记较轻或未标记。这可能反映了神经丝蛋白的酪氨酸残基主要定位于路易小体核心这一事实，并表明硝基酪氨酸存在于神经丝蛋白本身中。尽管这些观察结果尚无法在氧化应激与神经元功能障碍之间提供明确的联系，但它们表明在PD的易损神经元内发生了氧化应激，在神经退行性变的靶细胞内留下了神经元蛋白氧化修饰的永久标记。此外，这些观察结果在PD的易损神经元内提供了兴奋性毒性与氧化应激之间的潜在联系，并代表了与另外两种主要的年龄相关性神经退行性疾病——阿尔茨海默病和肌萎缩侧索硬化症——相同的发病机制。
