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15 - Neuroendocrine Aspects of the Molecular Chaperones ADNF and ADNP
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- 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
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- Book:
- Molecular Chaperones and Cell Signalling
- Published online:
- 10 August 2009
- Print publication:
- 18 July 2005, pp 251-262
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- Chapter
- Export citation
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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].