Function and Chemotypes of Human Hsp70 Chaperones

In humans, Hsp70 chaperones are ubiquitously expressed in the cytosol, endoplasmic reticulum and mitochondria. They fulfill important roles in protein folding and the protection of cells from stress. Different forms of Hsp70 have also been found to regulate specific signaling pathways, many related to cell death. Cancer cells are notably abnormally dependent on Hsp70 chaperones for their survival. The importance of Hsp70s as drug targets is increasingly being recognized, particularly as potential cancer therapeutics. This review surveys recent advances in understanding Hsp70 mechanisms and then moves to provide an overview of current efforts directed at inhibiting Hsp70s as a target in diseases such as cancer and neurodegenerative disease.