神经退行性变中的免疫信号转导。
Immune Signaling in Neurodegeneration.
机构信息
Boston Children's Hospital, F.M. Kirby Neurobiology Center, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Boston Children's Hospital, F.M. Kirby Neurobiology Center, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA, USA.
出版信息
Immunity. 2019 Apr 16;50(4):955-974. doi: 10.1016/j.immuni.2019.03.016.
Neurodegenerative diseases of the central nervous system progressively rob patients of their memory, motor function, and ability to perform daily tasks. Advances in genetics and animal models are beginning to unearth an unexpected role of the immune system in disease onset and pathogenesis; however, the role of cytokines, growth factors, and other immune signaling pathways in disease pathogenesis is still being examined. Here we review recent genetic risk and genome-wide association studies and emerging mechanisms for three key immune pathways implicated in disease, the growth factor TGF-β, the complement cascade, and the extracellular receptor TREM2. These immune signaling pathways are important under both healthy and neurodegenerative conditions, and recent work has highlighted new functional aspects of their signaling. Finally, we assess future directions for immune-related research in neurodegeneration and potential avenues for immune-related therapies.
中枢神经系统的神经退行性疾病逐渐使患者丧失记忆、运动功能和完成日常任务的能力。遗传学和动物模型的进步开始揭示免疫系统在疾病发病机制中的作用；然而，细胞因子、生长因子和其他免疫信号通路在疾病发病机制中的作用仍在研究中。在这里，我们回顾了最近与三种关键免疫途径相关的遗传风险和全基因组关联研究，以及发病机制中的新兴机制，这三种途径为生长因子 TGF-β、补体级联和细胞外受体 TREM2。在健康和神经退行性条件下，这些免疫信号通路都很重要，最近的工作强调了它们信号传递的新功能方面。最后，我们评估了神经退行性疾病中与免疫相关的研究的未来方向和免疫相关治疗的潜在途径。
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