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Department of Neurology and Department of Molecular Biology and
Pharmacology, Washington University School of Medicine, St. Louis,
Missouri 63110
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-1
-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.
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