Brennan Faith H, Lee John D, Ruitenberg Marc J, Woodruff Trent M
School of Biomedical Sciences, The University of Queensland, Brisbane 4072, Australia.
School of Biomedical Sciences, The University of Queensland, Brisbane 4072, Australia; Queensland Brain Institute, The University of Queensland, Brisbane 4072, Australia; Trauma, Critical Care and Recovery, Brisbane Diamantina Health Partners, The University of Queensland, Brisbane 4072, Australia.
Semin Immunol. 2016 Jun;28(3):292-308. doi: 10.1016/j.smim.2016.03.015. Epub 2016 Apr 3.
The recognition that complement proteins are abundantly present and can have pathological roles in neurological conditions offers broad scope for therapeutic intervention. Accordingly, an increasing number of experimental investigations have explored the potential of harnessing the unique activation pathways, proteases, receptors, complexes, and natural inhibitors of complement, to mitigate pathology in acute neurotrauma and chronic neurodegenerative diseases. Here, we review mechanisms of complement activation in the central nervous system (CNS), and explore the effects of complement inhibition in cerebral ischemic-reperfusion injury, traumatic brain injury, spinal cord injury, Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease and Huntington's disease. We consider the challenges and opportunities arising from these studies. As complement therapies approach clinical translation, we provide perspectives on how promising complement-targeted therapeutics could become part of novel and effective future treatment options to improve outcomes in the initiation and progression stages of these debilitating CNS disorders.
补体蛋白大量存在且在神经疾病中可发挥病理作用这一认识为治疗干预提供了广阔空间。相应地，越来越多的实验研究探索了利用补体独特的激活途径、蛋白酶、受体、复合物和天然抑制剂来减轻急性神经创伤和慢性神经退行性疾病病理的潜力。在此，我们综述中枢神经系统（CNS）中补体激活的机制，并探讨补体抑制在脑缺血再灌注损伤、创伤性脑损伤、脊髓损伤、阿尔茨海默病、肌萎缩侧索硬化症、帕金森病和亨廷顿病中的作用。我们考虑这些研究带来的挑战和机遇。随着补体疗法迈向临床转化，我们就有前景的补体靶向疗法如何成为未来新型有效治疗选择的一部分以改善这些使人衰弱的中枢神经系统疾病起始和进展阶段的预后提供观点。
