Bcl-2 promotes regeneration of severed axons in mammalian CNS.
Most neurons of the mammalian central nervous system (CNS) lose the ability to regenerate severed axons in vivo after a certain point in development. At least part of this loss in regenerative potential is intrinsic to neurons. Although embryonic retinal ganglion cells (RGCs) can grow axons into tectum of any age, most RGCs from older animals fail to extend axons into CNS tissue derived from donors of any age, including the embryonic tectum. Here we report that the proto-oncogene bcl-2 plays a key role in this developmental change by promoting the growth and regeneration of retinal axons. This effect does not seem to be an indirect consequence of its well-known anti-apoptotic activity. Another anti-apoptotic drug, ZVAD, supported neuronal survival but did not promote axon regeneration in culture. This finding could lead to new strategies for the treatment of injuries to the CNS.
Chen
D F
DF
Howard Hughes Medical Institute, Center for Learning and Memory, Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139, USA.
Schneider
G E
GE
Martinou
J C
JC
Tonegawa
S
S
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D020170:Caspase 1; D002452:Cell Count; D002470:Cell Survival; D016922:Cellular Senescence / Q000502:physiology; D002490:Central Nervous System / Q000166:cytology; D003546:Cysteine Endopeptidases; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D005260:Female; D017353:Gene Deletion; D015870:Gene Expression; D019254:Genes, bcl-2; D006579:Heterozygote; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009416:Nerve Regeneration / Q000235:genetics*; D009842:Oligopeptides / Q000494:pharmacology; D009924:Organ Culture Techniques; D012165:Retinal Ganglion Cells / Q000166:cytology; D013477:Superior Colliculi / Q000166:cytology / Q000196:embryology
D015853:Cysteine Proteinase Inhibitors; D009842:Oligopeptides; C103712:benzyloxycarbonyl-valyl-alanyl-aspartyl-fluoromethane; D003546:Cysteine Endopeptidases; D020170:Caspase 1