Abstract
We investigated the effect of long-term, peripheral treatment with enoxaparin, a low molecular weight heparin, in transgenic mice overexpressing human amyloid precursor protein(751). Enoxaparin (6 IU per mouse intraperitoneally, three times a week for 6 months) significantly lowered the number and the area occupied by cortical beta-amyloid deposits and the total beta-amyloid (1-40) cortical concentration. Immunocytochemical analysis of glial fibrillary acid protein-positive cells showed that enoxaparin markedly reduced the number of activated astrocytes surrounding beta-amyloid deposits. In vitro, the drug dose-dependently attenuated the toxic effect of beta-amyloid on neuronal cells. Enoxaparin dose-dependently reduced the ability of beta-amyloid to activate complement and contact systems, two powerful effectors of inflammatory response in AD brain. By reducing the beta-amyloid load and cytotoxicity and proinflammatory activity, enoxaparin offers promise as a tool for slowing the progression of Alzheimer's disease.
Publication types
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Research Support, Non-U.S. Gov't
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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Amyloid beta-Peptides / antagonists & inhibitors
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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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Animals
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Astrocytes / drug effects
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Astrocytes / metabolism
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Astrocytes / pathology
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Cerebral Cortex / drug effects
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Cerebral Cortex / metabolism
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Cerebral Cortex / pathology
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Complement Activation / drug effects
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Disease Models, Animal
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Dose-Response Relationship, Drug
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Enoxaparin / therapeutic use*
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Glial Fibrillary Acidic Protein / biosynthesis
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Heparin, Low-Molecular-Weight / therapeutic use*
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Male
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Mice
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Mice, Transgenic
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Neurons / drug effects
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Neurons / metabolism
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Neurons / pathology
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PC12 Cells
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Peptide Fragments / antagonists & inhibitors
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Peptide Fragments / metabolism
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Peptide Fragments / toxicity
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Plaque, Amyloid / drug effects*
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Plaque, Amyloid / pathology
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Rats
Substances
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Amyloid beta-Peptides
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Enoxaparin
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Glial Fibrillary Acidic Protein
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Heparin, Low-Molecular-Weight
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Peptide Fragments
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amyloid beta-protein (1-40)
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amyloid beta-protein (1-42)