Section Review: Central & Peripheral Nervous Systems: Therapeutic potential of calpain inhibitors in neurodegenerative disorders

Abstract

Pathologic activation of calpain has been linked to a number of degenerative conditions where cellular calcium overloading is involved. Inhibition of this protease would be very attractive from the therapeutic standpoint of minimal side-effects because it exists mainly as the inactive pro-enzyme form under normal physiological conditions. Moreover, the therapeutic window of this approach may be wider compared to ion channel and glutamate receptor antagonism for the treatment of ischaemia since calpain activation is further downstream in the pathogenic cascade. Although calpain was discovered thirty years ago, potent and selective inhibitors have only now become available. This article reviews the recent development of these inhibitors.

Key Words:

• Ca2+-dependent
• calpain
• hypoxia
• ischaemia
• neuroprotection
• protease
• protease inhibitor
• proteolysis