Kawamoto Yasuhiro, Ito Hidefumi, Ihara Masafumi, Takahashi Ryosuke
Department of Neurology, Faculty of Medicine, Kyoto University, Sakyoku, Kyoto, Japan.
Neuroreport. 2012 Feb 15;23(3):162-7. doi: 10.1097/WNR.0b013e32834f4066.
X-linked inhibitor of apoptosis protein (XIAP) blocks the apoptosis by binding to and inhibiting caspases-3, 7, and 9. XIAP is negatively regulated by the mitochondrial serine protease, HtrA2/Omi. The aim of this study was to investigate the role of XIAP and the relationship between XIAP and HtrA2/Omi in patients with Parkinson's disease or dementia with Lewy bodies. We conducted immunohistochemical studies on XIAP in formalin-fixed, paraffin-embedded sections from eight normal participants, 10 patients with Parkinson's disease, five patients with dementia with Lewy bodies, and seven patients with Alzheimer's disease, and then double-labeling immunohistochemistry for XIAP and HtrA2/Omi in sections from the Parkinson's disease and dementia with Lewy bodies cases. Brainstem-type and cortical Lewy bodies were intensely immunostained for XIAP, and XIAP immunoreactivity was localized to the halos of brainstem-type Lewy bodies and to the entire bodies of cortical Lewy bodies. Double immunofluorescence analyses showed that XIAP and HtrA2/Omi immunoreactivities were colocalized to both types of Lewy bodies. Our results suggest that XIAP may be partially associated with the pathogenesis of Parkinson's disease and dementia with Lewy bodies.
X连锁凋亡抑制蛋白(XIAP)通过结合并抑制半胱天冬酶-3、7和9来阻断细胞凋亡。XIAP受线粒体丝氨酸蛋白酶HtrA2/Omi的负调控。本研究的目的是探讨XIAP在帕金森病或路易体痴呆患者中的作用以及XIAP与HtrA2/Omi之间的关系。我们对8名正常参与者、10名帕金森病患者、5名路易体痴呆患者和7名阿尔茨海默病患者的福尔马林固定石蜡包埋切片进行了XIAP的免疫组织化学研究,然后对帕金森病和路易体痴呆病例的切片进行了XIAP和HtrA2/Omi的双重免疫组织化学标记。脑干型和皮质路易体对XIAP呈强免疫染色,XIAP免疫反应定位于脑干型路易体的晕圈和皮质路易体的整个体部。双重免疫荧光分析表明,XIAP和HtrA2/Omi免疫反应共定位于两种类型的路易体。我们的结果表明,XIAP可能与帕金森病和路易体痴呆的发病机制部分相关。