Mechanistic insights of molecular chaperone Hsp70: Pathogenesis of neurodegenerative diseases

Proper folding of a protein is essential for its diverse cellular functions. Improper protein folding may lead to the onset of various conformational diseases, including neurodegenerative diseases. Fortunately, multiple mechanisms maintain protein homeostasis in cells, where molecular chaperones perform critical functions. Chaperones are responsible for folding nascent proteins and directing aberrantly folded proteins for proteolytic clearance. Chaperones are considered the first defensive molecules against misfolded proteins. However, the identification of chaperones in disease-associated inclusion bodies signifies their involvement in the pathogenesis of neuronal degenerative diseases. Here, we highlight mechanistic insights into the role of heat shock protein 70 (Hsp70) molecular chaperones in several diseases such as Alzheimer’s, Parkinson’s, Huntington’s, and amyotrophic lateral sclerosis (ALS). Furthermore, we explore the different Hsp70-based molecular mechanisms implicated in neurodegeneration. Comprehensive information on these molecular mechanisms can aid in the development of better chaperone-based therapeutic strategies.