Dysregulation of Heat Shock Proteins in Neurodegenerative Diseases: Restorative Roles of Small Molecules and Natural Compounds

Abstract

Gradual depositions of misfolded amyloid proteins play major roles in onset, progression and severity of many neurodegenerative diseases. Several protein clearance machineries exist in the cell which are involved in degradation of these proteins. Therefore, these systems are considered the key players of cellular protein homeostasis. A molecular chaperone, such as heat shock protein (HSP) is one of them, which play a crucial role in degradation of these misfolded protein aggregates. Indeed, larger protein aggregates are degraded by phagocytosis or macroautophagy mechanism, whereas smaller protein aggregates are degraded within the lysosomes with the help of HSP or via ubiquitin proteosomal system. Importantly, the HSPs become dysregulated in different neurodegenerative diseases. Therefore, enhancement of cellular protein quality control machineries, specifically the levels and activities of molecular chaperones could suppress the misfolded protein aggregation and can restore cellular function. Several small molecules and natural polyphenols have been shown to maintain HSP levels in different neurodegenerative diseases. In this book chapter, we discuss the current understanding of the roles of HSPs in protein misfolding neurological diseases, especially on Alzheimer’s, Parkinson’s, Huntington’s, prion diseases and tauopathies. In addition, we also highlighted the modulatory roles of natural polyphenols on HSPs as a therapeutic strategy for protein misfolding neurological diseases.