Role of caspases in neuronal damage

There is growing evidence that neuronal apoptosis, or cell suicide, is likely to underlie a number of neurodegenerative disorders. The caspases are a growing family of cysteine proteases that execute the death program by proteolytic cleavage of a number of specific cellular substrates. Recent evidence suggests that they are also involved in processing of neurodegeneration-associated proteins such as amyloid precursor protein and huntingtin. Caspases could thus be attractive therapeutic targets in a number of neural pathologies. The challenge lies in understanding how and which caspases are important in neuronal apoptosis and processing of neurodegeneration-associated proteins and how they are normally regulated. Here we review the evidence for the involvement of caspases in neuronal damage and highlight various studies where caspase inhibition was effective in combating neuronal death.