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细胞溶质 DNA 感应 cGAS-STING 途径在神经退行性疾病中的作用。

The cytosolic DNA-sensing cGAS-STING pathway in neurodegenerative diseases.

机构信息

Department of Critical Care Medicine, Xijing Hospital, The Fourth Military Medical University, China.

Department of Intensive Care Unit, Joint Logistics Force No. 988 Hospital, Zhengzhou, China.

出版信息

CNS Neurosci Ther. 2024 Mar;30(3):e14671. doi: 10.1111/cns.14671.

Abstract

BACKGROUND

With the widespread prevalence of neurodegenerative diseases (NDs) and high rates of mortality and disability, it is imminent to find accurate targets for intervention. There is growing evidence that neuroimmunity is pivotal in the pathology of NDs and that interventions targeting neuroimmunity hold great promise. Exogenous or dislocated nucleic acids activate the cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS), activating the stimulator of interferon genes (STING). The activated STING triggers innate immune responses and then the cGAS-STING signaling pathway links abnormal nucleic acid sensing to the immune response. Recently, numerous studies have shown that neuroinflammation regulated by cGAS-STING signaling plays an essential role in NDs.

AIMS

In this review, we summarized the mechanism of cGAS-STING signaling in NDs and focused on inhibitors targeting cGAS-STING.

CONCLUSION

The cGAS-STING signaling plays an important role in the pathogenesis of NDs. Inhibiting the cGAS-STING signaling may provide new measures in the treatment of NDs.

摘要

背景

随着神经退行性疾病(NDs)的广泛流行以及高死亡率和残疾率,寻找准确的干预靶点迫在眉睫。越来越多的证据表明,神经免疫在 NDs 的发病机制中至关重要,针对神经免疫的干预措施具有巨大的潜力。外源性或脱位的核酸激活细胞质 DNA 传感器环鸟苷酸-腺苷酸合酶(cGAS),激活干扰素基因刺激物(STING)。激活的 STING 触发先天免疫反应,然后 cGAS-STING 信号通路将异常核酸感应与免疫反应联系起来。最近,许多研究表明,cGAS-STING 信号调节的神经炎症在 NDs 中起重要作用。

目的

在这篇综述中,我们总结了 cGAS-STING 信号在 NDs 中的作用机制,并重点介绍了针对 cGAS-STING 的抑制剂。

结论

cGAS-STING 信号在 NDs 的发病机制中起重要作用。抑制 cGAS-STING 信号可能为 NDs 的治疗提供新的措施。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a64c/10924111/a3ff46a6964a/CNS-30-e14671-g001.jpg

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