Protein misfolding and aggregation in neurodegenerative disorders: focus on chaperone-mediated protein folding machinery

Abstract

Proteins are delicate, versatile and structurally complex biomolecules which regulate fundamental processes of the cellular systems. They are synthesized as long stretches of amino acid chains and in order to achieve the functional state each polypeptide chain must be folded into unique 3-dimensional structure^[1]. However, proteins have a very narrow range of thermodynamically stable physiological environment inside the cells to achieve correct folding and to function^[2].. In addition, several chronic challenges such as aging related physiological changes, diseases and certain stress conditions also interfere with protein functioning^[2]. Therefore, how the cells manage their proteome and ensure their metastable conformations to retain the conformational flexibility in the ever changing cellular environment has emerged as a fundamental question in contemporary biomedical research.