Is caspase-3 inhibition a valid therapeutic strategy in cerebral ischemia?

Neurodegenerative diseases are characterized by progressive impairment of brain function as a consequence of ongoing neuronal cell death. Apoptotic mechanisms have been implicated in this process and a major involvement of caspase-3, a typical pro-apoptotic executioner protease, has been claimed. In this review, the role of caspase-3 in neuronal cell loss in animal models of stroke is discussed and critically evaluated. In summary, it is concluded that the biochemical evidence favoring caspase-3 as a therapeutic target in cerebral ischemia is not convincing, and the development of selective caspase-3 inhibitors for the treatment of human stroke must be viewed as high risk.