基因组不稳定是许多神经变性疾病和中枢神经系统（CNS）癌症发展和进展的关键推动因素。 DNA损伤响应的启动是维持基因组完整性和预防此类疾病的关键步骤。然而，这些反应的缺失或无法修复包括电离辐射或氧化应激在内的引起基因或线粒体DNA损伤的刺激，可能导致细胞质中自身DNA的累积。已知居民CNS细胞（例如星形胶质细胞和微胶质细胞）能够在认识专门的模式识别受体（PRRs）的病原体和损伤相关分子模式时产生关键的免疫介质，这是由CNS感染所致。最近，多个细胞内PRRs，包括环状GMP-AMP合成酶，干扰素γ诱导16，黑色素瘤2中缺失以及Z-DNA结合蛋白已被鉴定为细胞质DNA传感器，在胶质免疫反应中发挥关键作用，以应对传染性因子。有趣的是，最近显示这些核酸传感器已在周围细胞类型中识别内源性DNA并触发免疫反应。在本综述中，我们讨论了可用证据表明细胞质DNA传感器由居民CNS细胞表达，并可以调节其对自身DNA存在的响应。此外，我们还讨论了胶质细胞DNA传感器中介反应提供保护防止肿瘤发生的潜力，相对于可能引发或促进神经变性疾病的潜在有害神经炎症。决定胶质细胞检测细胞质DNA的机制以及每种通路在特定CNS疾病及其阶段中的相对作用，可能对我们理解这些疾病的发病机制至关重要，并可以用于开发新的治疗方法。© 2023 Suptela和Marriott版权所有。

Genomic instability is a key driving force for the development and progression of many neurodegenerative diseases and central nervous system (CNS) cancers. The initiation of DNA damage responses is a critical step in maintaining genomic integrity and preventing such diseases. However, the absence of these responses or their inability to repair genomic or mitochondrial DNA damage resulting from insults, including ionizing radiation or oxidative stress, can lead to an accumulation of self-DNA in the cytoplasm. Resident CNS cells, such as astrocytes and microglia, are known to produce critical immune mediators following CNS infection due to the recognition of pathogen and damage-associated molecular patterns by specialized pattern recognition receptors (PRRs). Recently, multiple intracellular PRRs, including cyclic GMP-AMP synthase, interferon gamma-inducible 16, absent in melanoma 2, and Z-DNA binding protein, have been identified as cytosolic DNA sensors and to play critical roles in glial immune responses to infectious agents. Intriguingly, these nucleic acid sensors have recently been shown to recognize endogenous DNA and trigger immune responses in peripheral cell types. In the present review, we discuss the available evidence that cytosolic DNA sensors are expressed by resident CNS cells and can mediate their responses to the presence of self-DNA. Furthermore, we discuss the potential for glial DNA sensor-mediated responses to provide protection against tumorigenesis versus the initiation of potentially detrimental neuroinflammation that could initiate or foster the development of neurodegenerative disorders. Determining the mechanisms that underlie the detection of cytosolic DNA by glia and the relative role of each pathway in the context of specific CNS disorders and their stages may prove pivotal in our understanding of the pathogenesis of such conditions and might be leveraged to develop new treatment modalities.Copyright © 2023 Suptela and Marriott.