Calpain-2 as a therapeutic target for acute neuronal injury

Calpains represent a family of neutral, calcium-dependent proteases, which modify the function of their target proteins by partial truncation. These proteases have been implicated in numerous cell functions, including cell division, proliferation, migration, and death. In the CNS, where calpain-1 and calpain-2 are the main calpain isoforms, their activation has been linked to synaptic plasticity as well as to neurodegeneration. This review will focus on the role of calpain-2 in acute neuronal injury and discuss the possibility of developing selective calpain-2 inhibitors for therapeutic purposes. Areas covered: This review covers the literature showing how calpain-2 is implicated in neuronal death in a number of pathological conditions. The possibility of developing new selective calpain-2 inhibitors for treating these conditions is discussed. Expert opinion: As evidence accumulates that calpain-2 activation participates in acute neuronal injury, there is interest in developing therapeutic approaches using selective calpain-2 inhibitors. Recent data indicate the potential use of such inhibitors in various pathologies associated with acute neuronal death. The possibility of extending the use of such inhibitors to more chronic forms of neurodegeneration is discussed.