Roles of osmolytes in protein folding and aggregation in cells and their biotechnological applications

Abstract Nature has selected osmolytes to protect intracellular macromolecules exposed to denaturing conditions and stabilize proteins. Osmolytes are small naturally occurring compounds that act as chemical chaperones under changing environmental conditions and in disease states, and are present in microorganisms, animals, and plants. In the intracellular environment osmolytes naturally accumulate at high concentrations when cells/tissues are exposed to stressful conditions, which is important because protein aggregation, misfolding, and destabilization underlie the pathogenesis of several life-threatening neurodegenerative disorders. The chaperone abilities of osmolytes suggests they may be therapeutically used for the treatment of several diseases associated with protein misfolding, and their abilities to protect proteins against denaturing stresses impinges on the fundamental problem of protein stabilization, which plagues the pharmaceutical industry, biotechnologists, and researchers. We hope that this review will encourage further research in this area and catalyze increased collaboration at the interface of chemistry and biology to decipher the mechanisms and roles of protein folding, misfolding and aggregation in the fields of health and disease.