Death of oligodendrocytes mediated by the interaction of nerve growth factor with its receptor p75.

Casaccia-Bonnefil P, Carter BD, Dobrowsky RT, Chao MV
Nature. 1996 383 (6602): 716-9

PMID: 8878481 · DOI:10.1038/383716a0

Members of the nerve growth factor (NGF) family promote the survival of neurons during development. NGF specifically activates the receptor trkA, initiating a signal transduction cascade which ultimately blocks cell death. Here we show that NGF can have the opposite effect, inducing the death of mature oligodendrocytes cultured from postnatal rat cerebral cortex. This effect was highly specific, because NGF had no effect on oligodendrocyte precursors and astrocytes. Other neurotrophins such as brain-derived neurotrophin factor (BDNF) and neurotrophin-3 (NT-3) did not induce cell death. NGF binding to mature oligodendrocytes expressing the p75 neurotrophin receptor, but not trkA, resulted in a sustained increase of intracellular ceramide and c-Jun amino-terminal kinase (JNK) activity, which are thought to participate in a signal transduction pathway leading to cell death. Taken together, these results indicate that NGF has the ability to promote cell death in specific cell types through a ligand-dependent signalling mechanism involving the p75 neurotrophin receptor.

MeSH Terms (18)

Animals Apoptosis Calcium-Calmodulin-Dependent Protein Kinases Cells, Cultured Ceramides Cerebral Cortex Enzyme Activation JNK Mitogen-Activated Protein Kinases Mitogen-Activated Protein Kinases Nerve Growth Factors Oligodendroglia Proto-Oncogene Proteins Rats Receptor, Nerve Growth Factor Receptor, trkA Receptor Protein-Tyrosine Kinases Receptors, Nerve Growth Factor Signal Transduction

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