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

Biomolecules. 2020 Jan 13;10(1):132. doi: 10.3390/biom10010132.

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.

Keywords: Alzheimer’s; Aβ aggregation; osmolytes; protein folding/misfolding.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / metabolism
  • Amino Acids / metabolism
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Brain / metabolism
  • Carbohydrate Metabolism
  • Drug Discovery
  • Excipients / metabolism
  • Humans
  • Methylamines / metabolism
  • Neurodegenerative Diseases / metabolism*
  • Protein Aggregates
  • Protein Aggregation, Pathological / metabolism*
  • Protein Folding*
  • Urea / metabolism

Substances

  • Amino Acids
  • Amyloid beta-Peptides
  • Excipients
  • Methylamines
  • Protein Aggregates
  • Urea