A novel peptide prevents death in enriched neuronal cultures

Regul Pept. 2000 Dec 22;96(1-2):39-43. doi: 10.1016/s0167-0115(00)00198-1.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Amino Acid Sequence
  • Amyloid beta-Peptides / pharmacology*
  • Animals
  • Animals, Newborn
  • Cell Death / drug effects*
  • Cell Survival / drug effects
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Glucose / deficiency
  • Homeodomain Proteins*
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / pharmacology*
  • Neuroglia / physiology
  • Neurons / cytology
  • Neurons / drug effects*
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacology*
  • Peptide Fragments / chemistry
  • Peptide Fragments / pharmacology*
  • Rats


  • Amyloid beta-Peptides
  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • Neuroprotective Agents
  • Peptide Fragments
  • amyloid beta-protein (25-35)
  • Glucose