A new concept in the pharmacology of neuroprotection.
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., beta-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.
Gozes
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Department of Clinical Biochemistry, Sackler School of Medicine, Tel Aviv University, Israel. igozes@post.tau.ac.il
Brenneman
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D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000494:pharmacology / Q000502:physiology*; D009457:Neuroglia / Q000502:physiology; D009479:Neuropeptides; D018696:Neuroprotective Agents; D009842:Oligopeptides; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology / Q000502:physiology*
D001057:Apolipoproteins E; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D018696:Neuroprotective Agents; D009842:Oligopeptides; C410622:activity-dependent neurotrophic factor; D014660:Vasoactive Intestinal Peptide