Fig. 5

The effects of targeting the intracellular environment of proteostasis. Glycerol has the ability to increase the hydration layer of the protein and the intramolecular hydrophobic bonding strength. This in turn allows the free movement of proteins in the crowded environment of the ER thereby preventing aggregation of proteins. Differing concentrations (0.1–1%) of DMSO in a cell may increase protein synthesis of the misfolded proteins or by possibly overwhelming the quality control system. Thapsigargin acts as an inhibitor of the Ca²⁺ ATP2A pump pump and increases cytosolic calcium, and in doing so results in an enhanced rescue of mutant proteins (Robben et al. 2006). Curcumin is a nontoxic natural constituent of turmeric spice and affects the Ca²⁺ ATP2A pump found on the ER plasma membrane. Curcumin inhibits the pumps ability to maintain a high ER Ca²⁺ level which disturbs the ability of ER molecular chaperones to target the misfolded protein for ERAD, hence, allows the mutant protein to exit the ER. Post-translational modifications of lipid modifications and glycosylation can be therapeutically targeted to support disulfide bond and glycoprotein formation to enhance the proteostasis network (Milhem 2015)