From the Systems Life Sciences (YS, KH, YM, NN) and Neuropathology (TM, YI), Department of Medical Life Systems, Faculty of Medical and Life Sciences, Doshisha University, Kyotanabe, Kyoto; Department of Neuropathology, Tokyo Metropolitan Institute of Gerontology (HH, SM); Laboratory of Systems Biology and Medicine, Research Center for Advanced Science and Technology, University of Tokyo (OK-A, HI, TH); and Institute of Immunology Co Ltd (OK-A), Tokyo; Health Research Institute, National Institute of Advanced Industrial Science and Technology, Ikeda, Osaka (YY, EN); and Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-ku, Sapporo (KT-N, HA), Japan.
J Neuropathol Exp Neurol. 2014 Jul;73(7):714-28. doi: 10.1097/NEN.0000000000000087.
DJ-1, the product of a causative gene of a familial form of Parkinson disease, undergoes preferential oxidation of Cys106 (cysteine residue at position 106) under oxidative stress. Using specific monoclonal antibodies against Cys106 oxidized DJ-1 (oxDJ-1), we examined oxDJ-1 immunoreactivity in brain sections from DJ-1 knockout and wild-type mice and in human brain sections from cases classified into different Lewy body stages of Parkinson disease and Parkinson disease with dementia. Oxidized DJ-1 immunoreactivity was prominently observed in neuromelanin-containing neurons and neuron processes of the substantia nigra; Lewy bodies also showed oxDJ-1 immunoreactivity. Oxidized DJ-1 was also detected in astrocytes in the striatum, in neurons and glia in the red nucleus, and in the inferior olivary nucleus, all of which are related to regulation of movement. These observations suggest the relevance of DJ-1 oxidation to homeostasis in multiple brain regions, including neuromelanin-containing neurons of the substantia nigra, and raise the possibility that oxDJ-1 levels might change during the progression of Lewy body-associated neurodegenerative diseases.
DJ-1 是家族性帕金森病的致病基因产物，在氧化应激下优先发生 Cys106（第 106 位半胱氨酸残基）氧化。使用针对 Cys106 氧化 DJ-1（oxDJ-1）的特异性单克隆抗体，我们检测了 DJ-1 敲除和野生型小鼠脑切片以及帕金森病和帕金森病伴痴呆不同路易体阶段分类的人类脑切片中的 oxDJ-1 免疫反应性。氧化 DJ-1 免疫反应性在含神经黑色素的神经元和黑质神经元突起中明显观察到；路易体也显示出 oxDJ-1 免疫反应性。在纹状体的星形胶质细胞、红核中的神经元和神经胶质细胞以及下橄榄核中也检测到氧化 DJ-1，所有这些都与运动调节有关。这些观察结果表明 DJ-1 氧化与包括黑质含神经黑色素神经元在内的多个脑区的内稳态有关，并提出 oxDJ-1 水平可能在路易体相关神经退行性疾病的进展过程中发生变化的可能性。
