Figure 8.

Schematic diagrams of the activation of TNF-α/NF-κB and NSM00191 function in RA patients. (A) The elevated levels of TNF-α initiate signaling transduction by interacting with the membrane receptor TNFR1. TNFR1 further interacts with TRADD and recruits TRAF2 and RIP to form a complex. This complex activates IKK2, enabling the phosphorylation of IκBα, eventually causing the release of NF-κB. The increased level of NF-κB in the cytoplasm then translocates to the nucleus and induces the transcription of a number of genes, such as cytokines, chemokines, immunoreceptors and cell adhesion molecules. At the transcriptional level, a microRNA known as miR-7-5p can specifically bind to the 3'-UTR of p65, a subunit of NF-κB. (B) A small molecule called NSM00191 specifically disrupts the interaction between TRADD and TRAF2, causing the inhibition of TRAF2 downstream signaling transduction, which eventually results in the transcriptional inhibition of NF-κB downstream targets.