Castellani R, Smith M A, Richey P L, Perry G
Department of Pathology (Neuropathology), University of Maryland, Baltimore 21201-1595, USA.
Brain Res. 1996 Oct 21;737(1-2):195-200. doi: 10.1016/0006-8993(96)00729-9.
Oxidative stress is well accepted as an important pathogenic factor in Parkinson disease, based largely on indirect evidence. Recently, we have developed antibodies that recognize specific advanced glycation end-products (anti-pentosidine and anti-pyrraline), protein modifications that are potentiated by oxidative stress in a process termed glycoxidation. We applied these antibodies immunocytochemically to affected regions in Parkinson disease and diffuse Lewy body disease brains. Additionally, we used antibodies to heme oxygenase-1, a putative marker of oxidative stress response. Immunoreactivity to pentosidine, pyrraline, and heme oxygenase-1 was seen in the substantia nigra of Parkinson disease and the neocortex of diffuse Lewy body disease. Heme oxygenase-1 was further demonstrated by immunoelectron microscopy in intimate association with filaments of cortical Lewy bodies. Immunolocalization of advanced glycation end-products and a marker of oxidative stress response induction provides evidence that glycoxidation and oxidative stress may be an important pathogenic factor in diseases characterized by Lewy body formation, and furthers the evidence that cytoskeletal proteins and their inclusions are susceptible to oxidative stress.
氧化应激作为帕金森病的一个重要致病因素已被广泛接受，这主要基于间接证据。最近，我们研发出了能够识别特定晚期糖基化终产物的抗体（抗戊糖苷和抗吡咯赖氨酸），这些蛋白质修饰在一个被称为糖氧化的过程中会因氧化应激而增强。我们将这些抗体用于帕金森病和弥漫性路易体病大脑中受影响区域的免疫细胞化学检测。此外，我们还使用了针对血红素加氧酶-1的抗体，它被认为是氧化应激反应的一个标志物。在帕金森病的黑质和弥漫性路易体病的新皮质中观察到了对戊糖苷、吡咯赖氨酸和血红素加氧酶-1的免疫反应性。通过免疫电子显微镜进一步证实，血红素加氧酶-1与皮质路易体的细丝紧密相关。晚期糖基化终产物的免疫定位以及氧化应激反应诱导标志物的检测提供了证据，表明糖氧化和氧化应激可能是路易体形成相关疾病的一个重要致病因素，进一步证明细胞骨架蛋白及其包涵体易受氧化应激影响。
