CALPAIN AS A NOVEL TARGET FOR TREATING ACUTE NEURODEGENERATIVE DISORDERS

Calpains are cytosolic, neutral proteases that normally exist in an in active or quiescent state. They require higher than normal levels of c alcium for activation which, once accomplished, lead to irreversible p roteolysis of numerous cytoskeletal, membrane-associated and regulator y proteins. Because of these characteristics, calpain is gaining atten tion as a potentially important pathogenic variable in ischemic neuron al death. This manuscript explores this hypothesis by briefly reviewin g current support for the role played by calpain in ischemic neurodege neration, and then discussing a series of recently published studies w hich: ?. offer further evidence for the hypothesis, and 2. provide dir ect support for the idea that selective inhibition of calpain can grea tly limit the neuronal damage that would normally occur following both global as well as focal brain ischemia. Thus, the data reviewed in th is manuscript support the ideas that unregulated activation and proteo lysis of intraneuronal calpain plays a significant role in the brain d amage that occurs following an ischemic event and that delivering sele ctive and membrane permeant calpain inhibitors to ischemic tissue may provide a powerfully effective therapeutic means of limiting neuronal damage.