Journal of Molecular Neuroscience

, Volume 14, Issue 1, pp 61–68

A new concept in the pharmacology of neuroprotection


    • Department of Clinical Biochemistry, Sackler School of MedicineTel Aviv University
  • Douglas E. Brenneman
    • Section on Developmental and Molecular Pharmacology, Laboratory of Developmental Neurobiology, National Institutes for Child Health and Human DevelopmentNational Institutes of Health

DOI: 10.1385/JMN:14:1-2:061

Cite this article as:
Gozes, I. & Brenneman, D.E. J Mol Neurosci (2000) 14: 61. doi:10.1385/JMN:14:1-2:061


Vasoactive intestinal peptide (VIP), originally discovered in the intestine as a peptide of 28 amino acids, was later found to be a major brain peptide having neuroprotective activities. To exert neuroprotective activity, VIP requires glial cells secreting neuroprotective proteins. Activity-dependent neurotrophic factor (ADNF) is a recently isolated factor secreted by glial cells under the action of VIP. This protein, isolated by sequential chromatographic methods, was named activity-dependent neurotrophic factor since it protected neurons from death associated with blockade of electrical activity. A fourteen-amino-acid fragment of ADNF (ADNF-14) and the more potent, nine-amino-acid derivative (ADNF-9), exhibit activity that surpasses that of the parent protein with regard to potency and a broader range of effective concentration. Furthermore, the peptides exhibit protective activity in Alzheimer’s disease-related systems (e.g., β-amyloid toxicity and apolipoprotein E deficiencies, genes that have been associated with Alzheimer’s disease onset and progression). ADNP is another glial mediator of VIP-associated neuroprotection. NAP, an eight-amino-acid peptide derived from ADNP (sharing structural and functional similarities with ADNF-9), was identified as the most potent neuroprotectant described to-date in an animal model of apolipoprotein E-deficiency (knock-out mice). These femtomolar-acting peptides form a basis for a new concept in pharmacology: femtomolar neuroprotection.

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© Humana Press Inc 2000