A Novel peptide prevents death in enriched neuronal cultures

We have recently cloned a novel protein (activity-dependent neuroprotective protein, ADNP) containing an 8-amino-acid, femtomolar-acting peptide, NAPVSIPQ (NAP). Here we show, for the first time, that NAP exerted a protective effect on glia-depleted neurons in culture. The number of surviving neurons was assessed in cerebral cortical cultures derived from newborn rats. In these cultures, a 24-h treatment with the β-amyloid peptide (the Alzheimer's disease associated toxin) induced a 30-40% reduction in neuronal survival that was prevented by NAP (10^-13-10^-11 M). Maximal survival was achieved at NAP concentrations of 10^-12 M. In a second set of experiments, a 5-day incubation period, with NAP added once (at the beginning of the incubation period) exhibited maximal protection at 10^-10 M NAP. In a third set of experiments, a 10-min period of glucose deprivation resulted in a 30-40% neuronal death that was prevented by a 24-h incubation with NAP. Glucose deprivation coupled with β-amyloid treatment did not increase neuronal death, suggesting a common pathway. We thus conclude, that NAP can prevent neurotoxicity associated with direct action of the β-amyloid peptide on neurons, perhaps through protection against impaired glucose metabolism. Copyright (C) 2000 Elsevier Science B.V.