Ischemic delayed neuronal death: Role of the cysteine proteases calpain and cathepsins

A few days after a transient brain ischemia, the pyramidal neurons in the cornu Ammonis (CA) 1 sector of the hippocampus undergo selective death, a process named delayed neuronal death (DND). Cell death may occur as necrosis and/or apoptosis, and both have been reported to take place in DND. The cell's decision between apoptosis and necrosis may depend on the strength of the insult, the balance of downstream signal transduction systems, and the expression level of pro‐ and anti‐apoptotic or necrotic factors. Cytosolic calcium (Ca2+) overload specifically occurs in the CA1 neurons after ischemia and thus is considered a common triggering event of the death cascade. As Ca2+ activates a wide array of intracellular enzymes, many Ca2+‐targeted enzymes have been implicated in DND. Among these, the present review will focus on the cysteine proteases calpain and cathepsins (B and L). In addition, their possible interactions with another family of cysteine proteases, caspases, will be discussed in relation to the cellular fate toward apoptosis or necrosis.