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F. Hoffmann-LaRoche Ltd., Pharma Division, Preclinical Research, Basel, Switzerland.
Nerve growth factor (NGF) has been demonstrated to support survival and differentiation of neuronal cells. Recently, a role of NGF in neuronal apoptosis has been suggested. NGF binds to tropomyosin receptor kinase A (TrkA) and to 75-kDa NGF receptor (p75NTR). TrkA is responsible for differentiation and survival, but p75NTR, a member of the death receptor family, seems to mediate the apoptotic effect of NGF. Here we demonstrate that NGF-but not neurotrophin-3 (NT-3) or brain-derived neurotrophic factor (BDNF)-induced apoptosis in p75NTR-expressing human neuroblastoma SK-N-MC cells. BDNF prevented NGF-induced apoptosis. NGF-induced apoptosis was accompanied by the release of NFkappaB p65 and the activation of stress-activated protein kinase/c-jun amino terminal kinase. Because p75NTR and NGF are upregulated in Alzheimer's disease, NGF/p75NTR might be involved in neuronal cell death related to the disease.
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