Department of Orthopaedic Surgery, Hamamatsu University School of Medicine, Shizuoka 431-3192, Japan.
Neurochem Int. 2010 Feb;56(3):387-93. doi: 10.1016/j.neuint.2009.11.005. Epub 2009 Nov 20.
Regulated intramembrane proteolysis (RIP) is one of the signaling pathways mediating information transfer from the extracellular to the intracellular domain. gamma-Secretase is an aspartyl protease of the RIP that cleaves the intramembrane region of type I integral membrane proteins, such as amyloid precursor protein (APP). Presenilin 1 (PS1) is the catalytic subunit of gamma-secretase and PS1 mutations cause Alzheimer's disease, spastic paraplegia and spinal cord atrophy. The biological function of PS1 in the spinal cord has not been fully elucidated. Thus, to clarify the involvement of RIP in spinal cord injury, we examined the expression of PS1, APP and amyloid-beta protein (Abeta) following rat spinal cord hemisection. Western blot analysis showed that PS1, APP and Abeta levels increased 1 day after spinal cord hemisection. Immunohistochemistry showed an increased number of PS1 immunopositive cells about 1mm from the lesion site. PS1, APP and Abeta double staining with cell-type specific markers showed colocalization of PS1 with axons in the white matter of the lesioned side. These findings suggest that RIP signaling occurs following rat spinal cord injury. In the future, the control of RIP may offer a new strategy for the treatment of spinal cord injury.
调节性跨膜蛋白水解（RIP）是介导细胞外到细胞内域信息传递的信号通路之一。γ-分泌酶是 RIP 的天冬氨酸蛋白酶，可切割 I 型整膜蛋白（如淀粉样前体蛋白（APP））的跨膜区域。早老素 1（PS1）是 γ-分泌酶的催化亚基，PS1 突变会导致阿尔茨海默病、痉挛性截瘫和脊髓萎缩。PS1 在脊髓中的生物学功能尚未完全阐明。因此，为了阐明 RIP 在脊髓损伤中的作用，我们研究了大鼠脊髓半切后 PS1、APP 和淀粉样β蛋白（Abeta）的表达情况。Western blot 分析显示，脊髓半切后 1 天 PS1、APP 和 Abeta 水平增加。免疫组织化学显示，损伤部位约 1mm 处 PS1 免疫阳性细胞数量增加。用细胞类型特异性标志物进行 PS1、APP 和 Abeta 双重染色显示 PS1 与损伤侧白质中的轴突共定位。这些发现表明 RIP 信号在大鼠脊髓损伤后发生。未来，RIP 的控制可能为脊髓损伤的治疗提供新策略。
