Why do mature CNS neurons of mammals fail to re-establish connections following injury--functions of bcl-2.
Factors inside and outside neurons control the process of axonal growth and regeneration. Recently, it has become apparent that neurons are determined intrinsically for their ability to grow axons. In the mammalian CNS, the intrinsic machinery of neurons that triggers the growth of axons during early embryonic stages is shut down at a certain point in development; as a consequence, axon elongation and regeneration cannot occur in postnatal life. The proto-oncogene Bcl-2 has been recognized to act as a key regulator for the program of axon elongation inside neurons. However, expressing the gene Bcl-2 in CNS neurons is not sufficient to induce nerve regeneration in the adult CNS, eliminating the inhibitory mechanism in the mature CNS environment is still required. Recently, the formation of glia scar has been reported to be the major limiting factor in the CNS environment that blocks nerve regeneration. These new discoveries challenge the classical view of nerve regeneration in the mammalian CNS. It opens up a new dimension in the study of the cellular and molecular mechanisms underlying neurodevelopmental and neurodegenerative diseases.
Chen
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DF
Howard Hughes Medical Institute, Center for Learning and Memory, Center for Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA. dfchen@wccf.mit.edu
Tonegawa
S
S
D000375:Aging; D000818:Animals; D001369:Axons / Q000502:physiology; D016923:Cell Death; D002470:Cell Survival; D002490:Central Nervous System / Q000166:cytology / Q000502:physiology*; D006801:Humans; D008322:Mammals; D009416:Nerve Regeneration; D019636:Neurodegenerative Diseases / Q000473:pathology / Q000503:physiopathology*; D009457:Neuroglia / Q000166:cytology / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2