McKnight Brain Institute, Center for Translational Research in Neurodegenerative Disease, Department of Neuroscience and Neurology, University of Florida, Gainesville, FL 32607, USA.
Neuron. 2019 Mar 20;101(6):1003-1015. doi: 10.1016/j.neuron.2019.02.027.
Immunoproteostasis is a term used to reflect interactions between the immune system and the proteinopathies that are presumptive "triggers" of many neurodegenerative disorders. The study of immunoproteostasis is bolstered by several observations. Mutations or rare variants in genes expressed in microglial cells, known to regulate immune functions, or both can cause, or alter risk for, various neurodegenerative disorders. Additionally, genetic association studies identify numerous loci harboring genes that encode proteins of known immune function that alter risk of developing Alzheimer's disease (AD) and other neurodegenerative proteinopathies. Further, preclinical studies reveal beneficial effects and liabilities of manipulating immune pathways in various neurodegenerative disease models. Although there are concerns that manipulation of the immune system may cause more harm than good, there is considerable interest in developing immune modulatory therapies for neurodegenerative disorders. Herein, I highlight the promise and challenges of harnessing immunoproteostasis to treat neurodegenerative proteinopathies.
免疫稳态是一个术语，用于反映免疫系统与蛋白病之间的相互作用，蛋白病被认为是许多神经退行性疾病的“触发因素”。免疫稳态的研究得到了几个观察结果的支持。在小胶质细胞中表达的、已知调节免疫功能的基因或两者的突变或罕见变异可导致或改变各种神经退行性疾病的风险。此外，遗传关联研究确定了许多含有已知具有免疫功能的蛋白质的基因的基因座，这些基因会改变患阿尔茨海默病 (AD) 和其他神经退行性蛋白病的风险。此外，临床前研究揭示了在各种神经退行性疾病模型中操纵免疫途径的有益效果和不利因素。尽管人们担心免疫系统的操纵可能弊大于利，但人们对开发治疗神经退行性疾病的免疫调节疗法仍有浓厚兴趣。在此，我强调利用免疫稳态来治疗神经退行性蛋白病的前景和挑战。
