Abstract
Amyloid-beta (Abeta) peptides, widely presumed to cause Alzheimer's disease, increased mouse neuronal expression of collagen VI through a mechanism involving transforming growth factor signaling. Reduction of collagen VI augmented Abeta neurotoxicity, whereas treatment of neurons with soluble collagen VI blocked the association of Abeta oligomers with neurons, enhanced Abeta aggregation and prevented neurotoxicity. These results identify collagen VI as an important component of the neuronal injury response and demonstrate its neuroprotective potential.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Alzheimer Disease / metabolism*
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Alzheimer Disease / pathology*
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Alzheimer Disease / physiopathology
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Amyloid beta-Peptides / genetics
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Amyloid beta-Peptides / metabolism*
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Animals
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Astrocytes / cytology
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Astrocytes / metabolism
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Collagen Type VI / genetics
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Collagen Type VI / metabolism*
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Dentate Gyrus / metabolism
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Dentate Gyrus / pathology
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Dentate Gyrus / physiopathology
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Humans
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Mice
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Mice, Transgenic
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Neurons / metabolism*
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Neurons / pathology
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Oligonucleotide Array Sequence Analysis
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Peptide Fragments / genetics
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Peptide Fragments / metabolism*
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Protein Binding / physiology
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Signal Transduction / physiology
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Transforming Growth Factor beta / metabolism
Substances
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Amyloid beta-Peptides
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Collagen Type VI
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Peptide Fragments
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Transforming Growth Factor beta
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amyloid beta-protein (1-42)