Propson Nicholas E, Gedam Manasee, Zheng Hui
Huffington Center on Aging, Baylor College of Medicine, Houston, Texas 77030, USA.
Interdepartmental Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.
Annu Rev Pathol. 2021 Jan 24;16:277-298. doi: 10.1146/annurev-pathol-031620-113409. Epub 2020 Nov 24.
Classic innate immune signaling pathways provide most of the immune response in the brain. This response activates many of the canonical signaling mechanisms identified in peripheral immune cells, despite their relative absence in this immune-privileged tissue. Studies over the past decade have strongly linked complement protein production and activation to age-related functional changes and neurodegeneration. The reactivation of the complement signaling pathway in aging and disease has opened new avenues for understanding brain aging and neurological disease pathogenesis and has implicated cell types such as astrocytes, microglia, endothelial cells, oligodendrocytes, neurons, and even peripheral immune cells in these processes. In this review, we aim to unravel the past decade of research related to complement activation and its numerous consequences in aging and neurological disease.
经典的固有免疫信号通路在大脑中提供了大部分免疫反应。尽管在这个免疫特权组织中相对缺乏,但这种反应激活了在外周免疫细胞中发现的许多典型信号机制。过去十年的研究有力地将补体蛋白的产生和激活与年龄相关的功能变化及神经退行性变联系起来。补体信号通路在衰老和疾病中的重新激活为理解脑衰老和神经疾病发病机制开辟了新途径,并在这些过程中涉及了星形胶质细胞、小胶质细胞、内皮细胞、少突胶质细胞、神经元甚至外周免疫细胞等细胞类型。在本综述中,我们旨在梳理过去十年中与补体激活及其在衰老和神经疾病中的众多影响相关的研究。