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 beta-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 beta-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 beta-amyloid peptide on neurons, perhaps through protection against impaired glucose metabolism.
Zemlyak
I
I
Department of Clinical Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, 69978, Tel Aviv, Israel.
Furman
S
S
Brenneman
D E
DE
Gozes
I
I
D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D016923:Cell Death / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000172:deficiency; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000494:pharmacology*; D009457:Neuroglia / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats
D016229:Amyloid beta-Peptides; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D005947:Glucose