Abstract
Amyloid beta (Abeta), the major component of the senile plaques of Alzheimer's disease, is implicated in neuronal cell death. We have found that Abeta42, a neurotoxic form of Abeta peptide, induces both neuronal and glial expression of TGFbeta2. We have further demonstrated that the addition into culture media of neutralizing antibody to TGFbeta2 or a large amount of the recombinant soluble amyloid precursor protein alpha, the extracellular domain of amyloid precursor protein (APP) generated by alpha secretase, suppresses death in primary cortical neurons (PCNs) induced by Abeta42 in vitro. Combined with the finding in our recent study indicating that TGFbeta2 is a neuronal cell death-inducing ligand for APP, it is suggested that TGFbeta2 is an autocrinal mediator for Abeta42-induced death in PCNs.
2006 Wiley-Liss, Inc.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Amyloid beta-Peptides / toxicity*
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Analysis of Variance
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Animals
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Blotting, Western / methods
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Cell Death / drug effects*
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Cell Line, Tumor
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Cerebral Cortex / cytology
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Drug Interactions
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Embryo, Mammalian
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / physiology
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Glioma
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Humans
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Immunohistochemistry / methods
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Mice
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Neuroblastoma
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Neurons / drug effects*
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Peptide Fragments / toxicity*
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Reverse Transcriptase Polymerase Chain Reaction / methods
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Time Factors
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Transforming Growth Factor beta / genetics
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Transforming Growth Factor beta / metabolism*
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Transforming Growth Factor beta2
Substances
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Amyloid beta-Peptides
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Peptide Fragments
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TGFB2 protein, human
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Transforming Growth Factor beta
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Transforming Growth Factor beta2
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amyloid beta-protein (1-42)