Apoptosis and cell death in neuronal cells: where does Ca2+ fit in?

Mounting evidence shows that neuronal death is an important and essential c omponent of brain tissue homeostasis, with two major forms of cell death oc curring. necrosis and apoptosis. No general consensus exists as to whether these two forms of neuronal death represent separate cellular processes or just two different forms of a common 'death pathway'. One difference betwee n them is the role played by intracellular Ca2+: central and obligatory, in necrosis and possible, but not always necessary in triggering apoptosis. F urthermore, the same assessment of the involvement of Ca2+ signalling could also distinguish between two possible apoptotic states in the nervous syst em: one, the 'developmental apoptosis', involving immature and developing n eurons, in which Ca2+ plays mainly an apo-protector role, and another one, associated mainly with pathological instances and involving fully matured a nd established neurons, in which Ca2+ plays an ape-inducing role.