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The Journal of Neuroscience, September 1, 2000, 20(17):6340-6346
Neurotrophins Induce Death of Hippocampal Neurons via the p75 Receptor
Wilma J. Friedman Department of Pathology, Taub Institute for the Study of Alzheimer's Disease and the Aging Brain, and the Center for Neurobiology and Behavior, Columbia University College of Physicians and Surgeons, New York, New York 10032
Nerve growth factor (NGF) and related neurotrophins influence neuronal survival and differentiation via interactions with the trk family of receptors. Recent studies have demonstrated that neurotrophins may also induce cell death via the p75 receptor. The importance and generality of neurotrophin-induced death in the brain have not been defined but may play a critical role during development and in disease-associated neuronal death. Here we demonstrate for the first time that all four members of the neurotrophin family directly elicit the death of hippocampal neurons via the p75 receptor. The hippocampus is a complex structure with many different neuronal subpopulations, and signals that influence neuronal death during development may have a critical impact on the mature function of this structure. In these studies we show that each neurotrophin causes the death of hippocampal neurons expressing p75 but lacking the cognate trk receptor. Neurotrophin-induced neuronal death is mediated by activation of Jun kinase. These studies demonstrate that neurotrophins can regulate death as well as survival of CNS neurons.
Key words: neurotrophins; NGF; neurotrophin receptors; p75; apoptosis; Jun kinase
Copyright © 2000 Society for Neuroscience 0270-6474/00/20176340-07$05.00/0
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