Fig. 1: Activation of cGAS-STING signaling pathway mediates the IVDD.

In degenerative discs, inflammation and cell death could liberate DNAs aberrantly. cGAS can identify the cytosolic DNA, transform ATP and GTP into the second messenger 2′,3′-cGAMP, and then bind to and enhance the activation of STING in the ER. After STING was transported to the Golgi apparatus, it could activate the downstream signaling pathway of TBK1-IRF3 and -NF-κB, and enhance the activity of IRF3 and NF-κB. With increased activity, IRF3 and NF-κB may enter the nucleus and play a role in elevating the expression of type-I IFN and pro-inflammatory cytokines, respectively.