Calpain: An Emerging Therapeutic Target

Abstract

Calpain was first found in the year 1964 as a calcium associated cysteine protease enzyme. Mostly, it is present in all the eukaryotes and other organism. Despite of being an enzyme calpain is involved in cellular organization rather than proteolytic digestion. For calpain activation, adequate concentration of calcium is required. Rest of the concentration they get from endoplasmic reticulum (ER), calcium influx during oxidative stress etc. In adverse condition calpain utilized all the excess calcium and activates molecular cascade involved in progression of various disease. Pathogenesis of every disease is highly protein specific such as in Alzheimer’s disease CDK5 and MAPK, phosphorylate Tau proteins in the brain. Further, Beclin 1, Bcl 2 and PGC-1α interfere with the mitochondrial function in heart resulting in abnormal functioning. Few studies have been suggesteddeactivation of calpain may ameliorate pathological conditions but still there are certain checkpoints which are still unexplored and need attention. Calpain has role in several pathological conditions but in this comprehensive review, we expect to cover how calpain is involved in the pathogenesis of neurodegenerative disorders, cardiovascular and cancer. This review also explained findings of different researchers on use of calpain inhibitors and impact of knocking down calpain gene in amelioration of pathogenesis. This advanced knowledge of mechanismand findings would be helpful for further development of calpain inhibitors for clinical use.