Abstract
Insulin-like growth factor-I (IGF-I) is a pleiotropic polypeptide with a wide range of actions in both central and peripheral nervous sytems. Over the past few years, we studied the trophic as well as neuromodulatory roles of IGF-I in the brain. Accumulated evidence indicates that IGF-I, apart from regulating growth and development, protects neurons against cell death induced by amyloidogenic derivatives, glucose or serum deprivation via the activation of intracellular pathways implicating phosphatidylinositide 3/Akt kinase, winged-helix family of transcription factor FKHRL1 phosphorylation or production of free radicals. The effects of IGF-I on neuroprotection, glucose metabolism and activity-dependent plasticity suggest the potential usefulness of this growth factor or related mimetics in the treatment of Alzheimer's disease and other neurodegenerative disorders.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Alzheimer Disease / drug therapy*
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Alzheimer Disease / metabolism
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Alzheimer Disease / pathology
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Animals
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Brain / drug effects
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Brain / metabolism
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Brain / pathology
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Humans
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Insulin / analogs & derivatives
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Insulin / metabolism
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Insulin-Like Growth Factor I / metabolism*
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Insulin-Like Growth Factor I / pharmacology*
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Neurons / drug effects
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Neurons / metabolism
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Neurons / pathology
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Neuroprotective Agents / metabolism*
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Neuroprotective Agents / pharmacology*
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Protein Serine-Threonine Kinases / drug effects*
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Protein Serine-Threonine Kinases / metabolism*
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Proto-Oncogene Proteins c-akt
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Proto-Oncogene Proteins*
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Signal Transduction / drug effects*
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Signal Transduction / physiology
Substances
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Insulin
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Neuroprotective Agents
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Proto-Oncogene Proteins
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Insulin-Like Growth Factor I
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AKT1 protein, human
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt