cGAS-STING 信号通路在神经退行性变、神经炎症和衰老中的作用。
Signaling by cGAS-STING in Neurodegeneration, Neuroinflammation, and Aging.
机构信息
The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
出版信息
Trends Neurosci. 2021 Feb;44(2):83-96. doi: 10.1016/j.tins.2020.10.008. Epub 2020 Nov 10.
Recognition of foreign or misplaced nucleic acids is one of the principal modes by which the immune system detects pathogenic entities. When cytosolic DNA is sensed, a signal is relayed via the cGAS-STING pathway: this involves the activation of cyclic GMP-AMP (cGMP-AMP) synthase (cGAS) and generation of the cyclic dinucleotide cGAMP, followed by the induction of stimulator of interferon genes (STING). The cGAS-STING pathway responds to viral, bacterial, and self-DNA. Whereas it generally mediates immune surveillance and is often neuroprotective, excessive engagement of the system can be deleterious. This is relevant in aging and age-related neurological diseases, where neuroinflammation contributes to disease progression. This review focuses on cGAS-STING signaling in aging, neurodegeneration, and neuroinflammation, and on therapeutic implications.
识别外来或错位的核酸是免疫系统检测病原体的主要方式之一。当细胞质 DNA 被检测到时，信号通过 cGAS-STING 途径传递：这涉及到环鸟苷酸-腺苷酸（cGMP-AMP）合酶（cGAS）的激活和环二核苷酸 cGAMP 的产生，随后诱导干扰素基因刺激物（STING）。cGAS-STING 途径对病毒、细菌和自身 DNA 作出反应。虽然它通常介导免疫监视，并且通常具有神经保护作用，但该系统的过度参与可能是有害的。这与衰老和与年龄相关的神经退行性疾病有关，其中神经炎症会促进疾病进展。这篇综述重点介绍 cGAS-STING 信号在衰老、神经退行性变和神经炎症中的作用，以及治疗意义。
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