Programmed Cell Death in Neurons: Focus on the Pathway of Nerve Growth Factor Deprivation-Induced Death of Sympathetic Neurons
- Department of Neurology and Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110
Abstract
Extensive programmed cell death (PCD) occurs in the developing nervous system. Neuronal death occurs, at least in part, because neurons are produced in excess during development and compete with each other for the limited amounts of the survival-promoting trophic factors secreted by target tissues. Neuronal death is apoptotic and utilizes components that are conserved in other PCD pathways. In this review, we discuss the mechanism of trophic factor-dependent neuronal cell death by focusing on the pathway of nerve growth factor (NGF) deprivation-induced sympathetic neuronal death. We describe the biochemical and genetic events that occur in NGF-deprived sympathetic neurons undergoing PCD. Participation of the Bcl-2 family of proteins and the interleukin-1β-converting enzyme family of proteases (caspases) in this and other models of neuronal death is also examined. The order and importance of these components during NGF deprivation-induced sympathetic neuronal death are discussed.
Footnotes
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Send reprint requests to: Dr. Eugene M. Johnson, Jr., Department of Molecular Biology and Pharmacology, Washington University School of Medicine, Box 8103, 660 S. Euclid Avenue, St. Louis, MO 63110. E-mail: ejohnson{at}pharmdec.wustl.edu
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↵1 M. Deshmukh and E. M. Johnson, Jr., unpublished observations.
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↵2 T. L. Deckwerth, R. M. Easton, C. M. Knudson, S. J. Korsmeyer, and E. M. Johnson, Jr., manuscript in preparation.
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↵3 M. Deshmukh and E. M. Johnson, Jr., unpublished observations.
- Abbreviations:
- PCD
- programmed cell death
- NGF
- nerve growth factor
- ROS
- reactive oxygen species
- SOD
- superoxide dismutase
- JNK
- c-jun/amino-terminal kinase
- ICE
- interleukin-1β-converting enzyme
- MAP
- mitogen-activated protein
- PI
- phosphatidylinositol
- PARP
- poly(ADP-ribose) polymerase
- SCG
- superior cervical ganglion
- DRG
- dorsal root ganglion
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- Accepted March 12, 1997.
- The American Society for Pharmacology and Experimental Therapeutics
