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

Abstract

Most of the neurological disorders in the brain are caused by the abnormal buildup of misfolded or aggregated proteins. Osmolytes are low molecular weight organic molecules usually built up in tissues at a quite high amount during stress or any pathological condition. These molecules help in providing stability to the aggregated proteins and protect these proteins from misfolding. Alzheimer’s disease (AD) is the uttermost universal neurological disorder that can be described by the deposition of neurofibrillary tangles, aggregated/misfolded protein produced by the amyloid β-protein (Aβ). Osmolytes provide stability to the folded, functional form of a protein and alter the folding balance away from aggregation and/or degradation of the protein. Moreover, they are identified as chemical chaperones. Brain osmolytes enhance the pace of Aβ aggregation, combine with the nearby water molecules more promptly, and avert the aggregation/misfolding of proteins by providing stability to them. Therefore, osmolytes can be employed as therapeutic targets and may assist in potential drug design for many neurodegenerative and other diseases.

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

“…Brain osmolytes improve the speed of Aβ aggregation, interact with neighboring water molecules more rapidly, and prevent the aggregation/misfolding of proteins by providing stability. 29 , 51 …”

Trehalose Effect on The Aggregation of Model Proteins into Amyloid Fibrils

“…Several advances are made to understand and get detailed insight into the structural basis and mechanism of amyloid fibrils formation, cytotoxicity and therapeutic approaches to combat them [21][22][23][24][25][26][27][28]. In particular, when considering results collected on trehalose in the context of protein fibrillation, attention has to be paid also to the external environment characterized by a defined ionic strength and subjected to a particular redistribution of water molecules in proximity of protein surfaces.…”

Protocol for assessment of the efficiency of CRISPR/Cas RNP delivery to different types of target cells

“…In addition to glycine, betaine and proline are often used as osmoportectors [ 66 ]. Therefore, we will optimize concentrations of these osmoprotectants too as described earlier with transduction plate layout represented in Tables 5 and 6 .…”