Caspase inhibitors as neuroprotective agents

Apoptotic neuronal cell death has been demonstrated to occur in the central nervous system (CNS), following both acute injury and during chronic neurodegenerative conditions. Currently, the majority of experimental evidence for a role of caspases in CNS damage has been established following acute neuronal insults, including ischaemic stroke, traumatic brain injury and spinal cord injury. In vitro and in vivo models have been used to demonstrate caspase activation, and treatment with available caspase inhibitors can provide significant protection. Overall, acute neuronal injury represents a major unmet medical need and caspase inhibitors may be an attractive approach to preserve neuronal function by extending the therapeutic window and providing long-term neuroprotection. Currently, several inhibitors are in preclinical drug development and this review summarises recent advances in the development of novel caspase inhibitors for the treatment of acute neuronal injury.