Kawamoto Yasuhiro, Ayaki Takashi, Urushitani Makoto, Ito Hidefumi, Takahashi Ryosuke
Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
J Neurol Sci. 2020 Aug 15;415:116928. doi: 10.1016/j.jns.2020.116928. Epub 2020 May 20.
HS1-associated protein X-1 (HAX-1) and presenilin-associated rhomboid-like protein (PALR) were reported to play an important role in the activation of HtrA2/Omi, which is also designated PARK13, in the mitochondria. To elucidate the role of HAX-1 and PARL in patients with Parkinson's disease (PD) and dementia with Lewy bodies (DLB), we performed immunohistochemical studies on HtrA2/Omi, HAX-1 and PARL using autopsied brains from 8 normal subjects, 10 patients with PD and 5 patients with DLB. In accordance with our previous report, brainstem-type and cortical Lewy bodies were strongly immunopositive for HtrA2/Omi. In the normal brains, HAX-1 and PARL immunoreactivities were observed in various types of neurons in the cerebral cortex, midbrain, and upper pons. HAX-1 and PARL immunoreactivities were also observed in the remaining neurons, and brainstem-type and cortical Lewy bodies were intensely immunoreactive for HAX-1 and PARL. Both immunoreactivities were localized to the halo or core of brainstem-type Lewy bodies. Our results suggest that brainstem-type and cortical Lewy bodies may contain HAX-1 and PARL as well as HtrA2/Omi, and that these proteins may partially contribute to the formation of Lewy bodies and may be associated with the pathogenesis of PD and DLB.
据报道，HS1相关蛋白X-1（HAX-1）和早老素相关类菱形蛋白（PALR）在激活线粒体中的HtrA2/Omi（也称为PARK13）过程中发挥重要作用。为了阐明HAX-1和PARL在帕金森病（PD）和路易体痴呆（DLB）患者中的作用，我们使用8名正常受试者、10名PD患者和5名DLB患者的尸检大脑，对HtrA2/Omi、HAX-1和PARL进行了免疫组织化学研究。根据我们之前的报告，脑干型和皮质路易体对HtrA2/Omi呈强免疫阳性。在正常大脑中，在大脑皮质、中脑和脑桥上段的各种类型神经元中观察到HAX-1和PARL免疫反应性。在其余神经元中也观察到HAX-1和PARL免疫反应性，并且脑干型和皮质路易体对HAX-1和PARL呈强烈免疫反应性。两种免疫反应性均定位于脑干型路易体的晕或核心。我们的结果表明，脑干型和皮质路易体可能同时含有HAX-1、PARL以及HtrA2/Omi，并且这些蛋白质可能部分促成路易体的形成，并且可能与PD和DLB的发病机制相关。
