Chapter Six Protein misfolding in endoplasmic reticulum stress with applications to renal diseases

Protein misfolding may be the result of a variety of different processes that disrupt the ability of a protein to form a thermodynamically stable tertiary structure that allows it to perform its proper function. In this chapter, we explore the nature of a protein's form that allows it to have a stable tertiary structure, and examine specific mutation that are known to occur in the coding regions of DNA that disrupt a protein's ability to be folded into a thermodynamically stable tertiary structure. We examine the consequences of these protein misfoldings in terms of the endoplasmic reticulum stress response and resulting unfolded protein response. These conditions are specifically related to renal diseases. Further, we explore novel therapeutics, pharmacological chaperones, that are being developed to alleviate the disease burden associated with protein misfolding caused by mutations. These interventions aim to stabilize protein folding intermediates and allow proper folding to occur as well as prevent protein aggregation and the resulting pathophysiological consequences.