Progress in understanding the role of cGAS-STING pathway associated with programmed cell death in intervertebral disc degeneration

Abstract Nucleus pulposus (NP) inflammatory response can induce intervertebral disc degeneration (IVDD) by causing anabolic and catabolic disequilibrium of the extracellular matrix (ECM). This process is accompanied by the production of endogenous DNAs, then detectable by the DNA sensor cyclic GMP-AMP synthase (cGAS). cGAS recognizes these DNAs and activates the downstream adaptor protein, a stimulator of interferon genes (STING), initiating a cascade of inflammation responses through various cytokines. This evidence implies a crucial role of the cGAS-STING signaling pathway in IVDD. Additionally, it is suggested that this pathway could modulate IVDD progression by regulating apoptosis, autophagy, and pyroptosis. However, a detailed understanding of the role of cGAS-STING pathway in IVDD is still lacking. This review provides a comprehensive summary of recent advances in our understanding of the role of the cGAS-STING pathway in modulating inflammatory response in IVDD. We delve into the connection between the cGAS-STING axis and apoptosis, autophagy, and pyroptosis in IVDD. Furthermore, we discuss the therapeutic potential of targeting the cGAS-STING signaling pathway in IVDD treatment. Overall, this review aims to provide a foundation for future directions in IVDD treatment strategies