Neuroprotection by caspase inhibitors

In the majority of brain diseases, apoptosis causes or exacerbates neuronal damage. Caspases are the final executioners of the apoptotic cell death programme. This family of proteases is implicated in the pathogenesis of many forms of brain damage, including those induced by ischaemia, inflammation or trauma, as well as those arising in Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis and epilepsy. Collectively, these conditions affect more than 10 m people in the USA alone. Apoptosis can be blocked by agents that inhibit caspase activity; these inhibitors have therapeutic benefit in the treatment of several model systems of brain diseases. In this review we focus on recent advances and summarise current knowledge concerning the use of these cell death inhibitors in neuroprotection.