BCL-2 PROMOTES REGENERATION OF SEVERED AXONS IN MAMMALIAN CNS

Most neurons of the mammalian central nervous system (CNS) lose the ab ility to regenerate severed axons in vivo after a certain point in dev elopment(1). At least part of this loss in regenerative potential is i ntrinsic to neuron(2-4). Although embryonic retinal ganglion cells (RG Cs) can grow axons into tectum of any age, most RGCs from older animal s fail to extend axons into CNS tissue derived from donors of any age, including the embryonic tectum(2). Here we report that the proto-onco gene bcl-2 plays a key role in this developmental change by promoting the growth and regeneration of retinal axons. This effect does not see m to be an indirect consequence of its well-known anti-apoptotic activ ity. Another anti-apoptotic drug, ZVAD, supported neuronal survival bu t did noe promote axon regeneration in culture. This finding could lea d to new strategies for the treatment of injuries to the CNS.