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Roles of cGAS in pulmonary pathophysiology: a multifaceted regulator and an emerging therapeutic target
Jiaxi Chen1, Shengda Wang1, Peiyu Yan2
1School of Pharmaceutical Sciences, Nanjing Tech University, 30 Puzhu South Road, Nanjing 211816, People's Republic of China; College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, 30 Puzhu South Road, Nanjing 211816, People's Republic of China.
Abstract:
Pulmonary diseases encompass a heterogeneous group of conditions, including pneumonia, lung injury, pulmonary fibrosis, and lung cancer. Although their etiologies are complex, a common denominator is that cytoplasmic DNA from pathogens, mitochondria, and the nucleus is a significant contributor to disease development. Cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase (cGAS) is a critical enzyme sensing cytosolic DNA fragments. Emerging evidence indicates that cGAS participates in the physiological and pathophysiological processes of pulmonary diseases by orchestrating cellular homeostasis and the immune response. This review describes structural and functional features of cGAS, explores its manifold influences on pulmonary pathologies, and summarizes advances in chemical regulation of cGAS activity. As a potentially valuable therapeutic target, cGAS warrants further investigation to elucidate its regulatory mechanisms in pulmonary diseases and to assess the clinical feasibility of cGAS-targeted drugs.
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