Abstract
An 8-amino-acid peptide, NAPVSIPQ (NAP), was identified as the smallest active element of activity-dependent neuroprotective protein that exhibits potent neuroprotective action. Potential signal transduction pathways include cGMP production and interference with inflammatory mechanisms, tumor necrosis factor-alpha, and MAC1-related changes. Because of its intrinsic structure, NAP might interact with extracellular proteins and also transverse membranes. NAP-associated protection against oxidative stress, glucose deprivation, and apoptotic mechanisms suggests interference with fundamental processes. This paper identifies p53, a key regulator of cellular apoptosis, as an intracellular target for NAP's activity.
Copyright 2004 Humana Press Inc.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Alzheimer Disease / drug therapy*
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Alzheimer Disease / physiopathology
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Alzheimer Disease / prevention & control
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Animals
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Apoptosis / drug effects
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Apoptosis / physiology
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Brain / drug effects*
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Brain / metabolism
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Brain / physiopathology
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Brain Ischemia / metabolism
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Brain Ischemia / prevention & control
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Cyclic GMP / metabolism
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Down-Regulation / drug effects
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Down-Regulation / physiology
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Encephalitis / drug therapy*
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Encephalitis / physiopathology
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Encephalitis / prevention & control
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Macrophage-1 Antigen / drug effects
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Macrophage-1 Antigen / metabolism
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Neuroprotective Agents / pharmacology*
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Neuroprotective Agents / therapeutic use
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Oligopeptides / pharmacology*
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Oligopeptides / therapeutic use
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Oxidative Stress / drug effects
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Oxidative Stress / physiology
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PC12 Cells
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Rats
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Tumor Necrosis Factor-alpha / drug effects
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Tumor Necrosis Factor-alpha / metabolism
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Tumor Suppressor Protein p53 / drug effects*
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Tumor Suppressor Protein p53 / metabolism
Substances
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Macrophage-1 Antigen
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Neuroprotective Agents
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Oligopeptides
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Tumor Necrosis Factor-alpha
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Tumor Suppressor Protein p53
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davunetide
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Cyclic GMP