Figure 1.

Stress processes involved in mutant-COMP pathology. This schematic briefly summarizes the pathologic processes in PSACH chondrocytes. Mutant-COMP is a pentamer; mutant subunits are shown in red, and wild type is shown in blue. Quality control systems recognize mutant-COMP as improperly folded, and it is held in the ER [47]. This accumulation generates ER stress that leads to oxidative stress and inflammation, and each makes the other stress worse [10]. Prolonged ER stress results in TNFα/TRAIL and CHOP activation that, in turn, elevate mTORC1 signaling, blocking autophagy—thereby preventing the clearance of the ER [11,27]. Orange bar block (⊥) represents inhibition associated with resveratrol and CurQ+, including inflammation, TNFα, oxidative stress, ER stress, PERK, and CHOP [10,12,13,17,18,48].