Calpain Inhibition: A Potential Therapeutic Target for Neurodegenerative and Neuromuscular Disorders

Author(s): Getaw Worku Hassen, Leo Kesner, Alfred Stracher and Abraham Shulman

Pp: 33-71 (39)

* (Excluding Mailing and Handling)

Abstract

Proteases are involved in different neurodegenerative and neuromuscular disorders. The role of protease inhibitors as therapeutic agents has been the matter of intense research. Given the role of proteases in these diseases, it is appealing to develop a single agent as a “magic bullet” that would target all the disease states. Calpain inhibitors have been tested with success in animal models of human diseases. In this review, we summarize the role of calpain in selected neurodegenerative and neuromuscular diseases. We describe the various instances in which calpain has been implicated and discuss the results of calpain inhibition in each disease entity as well as how targeted calpain inhibition could be beneficial. The focus of this review is to highlight the potential role of targeted inhibition as a therapeutic option and to introduce three newer calpain inhibitors with unique characteristics.

Keywords: Calcium, Calpain, Calpain inhibitors, CNS, Cyclin-dependent kinase, Excitotoxicity, Muscular dystrophy, Neurodegeneration, Targeted-calpain inhibition.