Abstract
The ability of galantamine (Reminyl) to inhibit the aggregation and toxicity of the beta-amyloid peptide (Abeta) was investigated. Galantamine showed concentration-dependent inhibition of aggregation of both Abeta 1-40 and Abeta 1-42, as determined by an ELISA method. Electron microscope studies of Abeta 1-40 incubated in the presence of galantamine revealed fibrils that were disordered and clumped in appearance. MTT and lactate dehydrogenase assays, employing SH-SY5Y human neuroblastoma cells, showed that galantamine reduced the cytotoxicity induced by Abeta 1-40. Galantamine also dramatically reduced Abeta 1-40-induced cellular apoptosis in these cells. There is some evidence that galantamine may not be acting purely as a symptomatic treatment. Disease-modifying effects of the drug could be due to an additional effect on Abeta aggregation and/or toxicity.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amyloid beta-Peptides / drug effects*
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Amyloid beta-Peptides / metabolism
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Amyloid beta-Peptides / toxicity
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Analysis of Variance
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Apoptosis / drug effects
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Cell Line, Tumor
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Cholinesterase Inhibitors / chemistry
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Cholinesterase Inhibitors / pharmacology*
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Dose-Response Relationship, Drug
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Enzyme-Linked Immunosorbent Assay
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Galantamine / chemistry
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Galantamine / pharmacology*
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Humans
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L-Lactate Dehydrogenase / metabolism
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Microscopy, Electron
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Models, Molecular
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Neuroprotective Agents / chemistry
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Neuroprotective Agents / pharmacology*
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Nuclear Magnetic Resonance, Biomolecular
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Peptide Fragments / drug effects*
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Peptide Fragments / metabolism
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Peptide Fragments / toxicity
Substances
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Amyloid beta-Peptides
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Cholinesterase Inhibitors
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Neuroprotective Agents
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Peptide Fragments
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amyloid beta-protein (1-40)
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amyloid beta-protein (1-42)
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Galantamine
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L-Lactate Dehydrogenase