Role of sugar osmolytes and their nano-counterparts as inhibitors in protein fibrillation

Protein aggregation is responsible for various human diseases, i.e. Alzheimer's, Parkinson's, Huntington's as well as cataract. Finding molecular drugs which could prevent protein aggregation at an initial state, reducing protein aggregate toxicity, delivering medications to distant organs and intracellular spaces, removing mature protein aggregates from cells, and designing efficient therapeutic approaches are the main issues. Various antiamyloidogenic micro/macro-molecules and nanomaterials were identified recently. Among all of them, osmolytes are dearer to us owing to their compatibility with the structure and function of the proteins that impart stability to proteins and protect them from aggregation. Sugars osmolytes (e.g. sucrose, trehalose, maltose, fructose, etc.) revealed a strong inhibitory action against in vitro amyloid fibrillogenesis/aggregation and stabilized aggregation-prone proteins such as & alpha;-synuclein, & beta;-amyloid peptides, insulin, and V & lambda;6 proteins. All of these anti-amyloidogenic materials still need improvement for better performance and appropriate therapeutic approaches are necessary for successful drug development. In this review, we explain how properly designing sugar molecules into colloidal and nanoparticle forms can significantly improve their performance. Furthermore, we demonstrate on the basis of available literature that sugar nanoparticle's anti-amyloidogenic activity can be improved upto many folds by modifying them to colloidal nanoparticles. Precisely, we described that such improved performance was owing to amplified bioavailability at intra and extracellular space, integrated binding property with protein, and better brain delivery option in nanoparticle form. Finally, we covered the possibility of designing a wide range of colloidal nanoparticles to prevent, dissolve, or remove protein aggregates.