Department of Neurology, Kansai Medical University, Hirakata, Japan.
Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Neuropathol Appl Neurobiol. 2018 Oct;44(6):563-573. doi: 10.1111/nan.12460. Epub 2018 Feb 7.
The human epidermal growth factor receptor family consists of four members that belong to the ErbB lineage of proteins (ErbB1-4). Neuregulin-1 (NRG1)/ErbB signalling regulates brain development and function. Abnormalities in this signalling have been implicated in the aetiology or development of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. So, we aimed at investigating whether the expression of NRG1 or ErbB proteins are altered in progressive supranuclear palsy (PSP).
The brains of 10 PSP and six control patients were investigated by immunohistochemical analysis.
Whereas C-terminal ErbB4 immunoreacitivity was partially but distinctly present in the cytoplasm and/or in the nucleus of neurons in control patients, it was rarely observed in the neuronal nuclei in PSP patients. In contrast, neurofibrillary tangles, coiled bodies and threads were robustly immunoreactive for C-terminal ErbB4 in PSP. Double immunofluorescence for C-terminal ErbB4 and phospho-tau revealed co-localization of these proteins within neuronal and glial inclusions. To the contrary, there was no difference in the subcellular localization of NRG1, ErbB1, ErbB2, and N-terminal ErbB4 between control and PSP patients. These proteins were localized in the cytoplasm of neurons.
Our present results suggest that NRG1/ErbB4 signalling could be an important event in the pathogenesis of PSP.
人类表皮生长因子受体家族由四个成员组成，属于 ErbB 蛋白家族（ErbB1-4）。神经调节蛋白-1（NRG1）/ErbB 信号调节大脑发育和功能。该信号的异常与神经退行性疾病（如阿尔茨海默病、帕金森病和肌萎缩侧索硬化症）的病因或发展有关。因此，我们旨在研究神经调节蛋白-1或 ErbB 蛋白的表达是否在进行性核上性麻痹（PSP）中发生改变。
通过免疫组织化学分析研究了 10 例 PSP 和 6 例对照患者的大脑。
尽管在对照组患者的神经元细胞质和/或核中部分但明显存在 C 末端 ErbB4 免疫反应性，但在 PSP 患者的神经元核中很少观察到。相比之下，神经原纤维缠结、卷曲体和线在 PSP 中对 C 末端 ErbB4 具有很强的免疫反应性。C 末端 ErbB4 和磷酸化 tau 的双重免疫荧光显示这些蛋白在神经元和神经胶质包含物内共定位。相反，NRG1、ErbB1、ErbB2 和 N 末端 ErbB4 在对照组和 PSP 患者之间的亚细胞定位没有差异。这些蛋白定位于神经元的细胞质中。
我们目前的结果表明，NRG1/ErbB4 信号可能是 PSP 发病机制中的一个重要事件。
