Role of Osmolytes in Amyloidosis

Abstract

Osmolytes are naturally occurring small organic molecules present in all kingdoms of life. These organic molecules are accumulated by living systems to circumvent stress conditions. A number of human diseases have been grouped under the protein-misfolding diseases. These entire diseases share the same hallmarks of the presence of cellular inclusions and plaques that are deposited in the cells and tissues affected by the disease. These misfolded forms of protein are responsible for initiating toxic cascades in the cell, causing vesicle dystrafficking, synaptic and cell organelle dysfunction, and ultimately cell death. Published results suggest that cells regulate many biological processes such as protein folding, protein disaggregation, and protein-protein interactions via accumulation of specific osmolytes. Since, as of now, complete cure for these protein-misfolding disorders does not exist; therefore, it becomes increasingly important to review the recent works on this aspect to develop strategies for therapeutics. It has been shown that certain osmolytes can prevent the proteins from misfolding. Thus, osmolytes can be utilized as therapeutics for such diseases. In this review article, we discuss the role of naturally occurring osmolytes in various forms of amyloidosis associated with human diseases.

Biophysical Elucidation of Fibrillation Inhibition by Sugar Osmolytes in α-Lactalbumin: Multispectroscopic and Molecular Docking Approaches

“…Osmolytes would be of immense significance for application in a large number of human diseases. Since osmolytes are accumulated under different disease conditions, identifying specific osmolytes concerning upregulation or downregulation in the cell under particular diseases will be useful for the selective use of osmolytes against the disease. , Osmolytes provide stability to the folded, functional shape of the protein and change the folding balance away from aggregation or protein degradation. They are often known as chemical chaperones.…”

Osmolytes: A Possible Therapeutic Molecule for Ameliorating the Neurodegeneration Caused by Protein Misfolding and Aggregation

“…They observed that TMAO, sorbitol, and glycerol resulted in lowering the rate of fibril production by reducing the progression of the unfolding of monomers. The above-mentioned investigational results have indicated an excellent link through volume segregation principle relevant to polymer crowding [38].…”

“…The alteration in AQP2 (aquaporin-2) gene causes misfolding of AQP-2 protein that may lead to developing diabetes insipidus in mammals. However, as soon as osmolytes like glycerol (1M) were supplemented in the cell culture medium, glycerol re-established the folded arrangement and consequently the appropriate reshuffle of this protein in the cell [37,38].…”

Nano-Osmolyte Conjugation: Tailoring the Osmolyte-Protein Interactions at the Nanoscale

“…Moreover, Ignatova et al have shown that since proline contains charged groups, it might induce electrostatic repulsion on interacting with a polypeptide chain at the start of protein aggregation . For example, proline at higher concentrations has been reported to encourage folding and inhibit aggregation of bovine carbonic anhydrase and lysozyme. , Among many osmolytes, trehalose, sorbitol, arginine, glycine-betaine, TMAO, and proline are industrially important osmolytes that prevent the protein misfolding from aggregation (Figure ). It has been found that trehalose, sorbitol, and arginine are effective excipients for the formulation and purification of therapeutic proteins. , Many neurological diseases are associated with the progressive accumulation of misfolded or aggregated proteins in the brain .…”