Journal of Molecular Neuroscience

, Volume 14, Issue 1, pp 61–68

A new concept in the pharmacology of neuroprotection


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

Authors and Affiliations

  1. 1.Department of Clinical Biochemistry, Sackler School of MedicineTel Aviv UniversityTel AvivIsrael
  2. 2.Section on Developmental and Molecular Pharmacology, Laboratory of Developmental Neurobiology, National Institutes for Child Health and Human DevelopmentNational Institutes of HealthBethesdaUSA