Calpain inhibitors as potential treatment for stroke and other neurodegenerative diseases: recent trends and developments

Abstract

Calpain, a calcium-activated cysteine protease present in most mammalian tissues, including the brain, has been implicated in neurodegenerative processes resulting from its overactivation following cerebral ischaemia or traumatic injury to the head or spinal cord. Through significant effort, particularly over the past ten to fifteen years, the complex biochemistry and physiological roles of this important regulatory enzyme have been partially clarified. Despite remarkable advances in understanding calpain’s normal functions, as well as its involvement in neuropathological conditions, a full appreciation of its role in neuronal cells remains elusive. A wide array of peptidic, peptide mimetic and non-peptide inhibitors have recently emerged, some of which display potency both in vitro and in vivo in various cell lines and animal models of focal and global ischaemia. A drug candidate has yet to be identified for advancement to clinical testing.

• calpain
• cysteine protease
• ischaemia
• neurodegeneration
• stroke