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  • Cited by 3
  • Print publication year: 2005
  • Online publication date: August 2009

15 - Neuroendocrine Aspects of the Molecular Chaperones ADNF and ADNP

    • By Illana Gozes, Department of Clinical Biochemistry and Interdepartmental Core Facility, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel, Inna Vulih, Department of Clinical Biochemistry and Interdepartmental Core Facility, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel, Irit Spivak-Pohis, Department of Clinical Biochemistry and Interdepartmental Core Facility, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel, Sharon Furman, Department of Clinical Biochemistry and Interdepartmental Core Facility, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
  • Edited by Brian Henderson, University College London, A. Graham Pockley, University of Sheffield
  • Publisher: Cambridge University Press
  • DOI: https://doi.org/10.1017/CBO9780511546310.016
  • pp 251-262

Summary

Introduction

Vasoactive intestinal peptide (VIP), which was originally discovered in the intestine as a 28–amino acid peptide and shown to induce vasodilation, was later found to be a major brain peptide with neuroprotective activities in vivo [1–5]. To exert neuroprotective activity in the brain, VIP requires glial cells that secrete protective proteins such as activity-dependent neurotrophic factor (ADNF [6]). ADNF, isolated by sequential chromatographic methods, was named activity-dependent neurotrophic factor because it protects neurons from death associated with the blockade of electrical activity.

ADNF is a 14-kDa protein, and structure-activity studies have identified femtomolar-active neuroprotective peptides, ADNF-14 (VLGGGSALLRSIPA) [6] and ADNF-9 (SALLRSIPA) [7]. ADNF-9 exhibits protective activity in Alzheimer's disease–related systems (β-amyloid toxicity [7], presenilin 1 mutation [8], apolipoprotein E deficiencies [9] – genes that have been associated with the onset and progression of Alzheimer's disease (AD)). Other studies have indicated protection against oxidative stress via the maintenance of mitochondrial function and a reduction in the accumulation of intracellular reactive oxygen species [10]. In the target neurons, ADNF-9 regulates transcriptional activation associated with neuroprotection (nuclear factor-κB [11]), promotes axonal elongation through transcriptionally regulated cAMP-dependent mechanisms [12] and increases chaperonin 60 (Cpn60/Hsp60) expression, thereby providing cellular protection against the β-amyloid peptide [13].

Longer peptides that include the ADNF-9 sequence (e.g., ADNF-14) activate protein kinase C and mitogen-associated protein kinase kinase and protect developing mouse brain against excitotoxicity [14].

Notes Added in Proof
Divinski, I, Mittelman, L and Gozes, I. A femtomolar acting octapeptide interacts with tubulin and protects astrocytes against zinc intoxication. J Biol Chem 2004, 279: 28531–28538
Gozes, I and Divinski, I. The femtomolar-acting NAP interacts with microtubules: Novel aspects of astrocyte protection. J Alzheimers Dis 2004, 6: S37–S41
Furman, S, Steingart, R A, Mandel, S, Hauser, J M, Brenneman, D E and Gozes, I. Subcellular localization and secretion of activity-dependent neuroprotective protein in astrocytes. Neuron Glia Biology 2005, in press
Brenneman, D E, Spong, C Y, Hauser, J M, Abebe, D, Pinhasov, A, Golian, T and Gozes, I. Protective peptides that are orally active and mechanistically nonchiral. J Pharmacol Exp Ther 2004, 309: 1190–1197
Wilkemeyer, M F, Chen, S Y, Menkari, C E, Sulik, K K and Charness, M E. Ethanol antagonist peptides: structural specificity without stereospecificity. J Pharmacol Exp Ther 2004, 309: 1183–1189
Zhou, F C, Sari, Y, Powrozek, T A and Spong, C Y. A neuroprotective peptide antagonizes fetal alcohol exposure-compromised brain growth. J Mol Neurosci 2004, 24: 189–199
Chiba, T, Hashimoto, Y, Tajima, H, Yamada, M, Kato, R, Niikura, T, Terashita, K, Schulman, H, Aiso, S, Kita, Y, Matsuoka, M and Nishimoto, I. Neuroprotective effect of activity-dependent neurotrophic factor against toxicity from familial amyotrophic lateral sclerosis-linked mutant SOD1 in vitro and in vivo. J Neurosci Res 2004, 78: 542–552
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