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Systematic in vivo ...
Systematic in vivo analysis of the intrinsic determinants of amyloid Beta pathogenicity.
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- Luheshi, Leila M (author)
- Department of Chemistry, University of Cambridge
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- Tartaglia, Gian Gaetano (author)
- Department of Chemistry, University of Cambridge
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- Brorsson, Ann-Christin (author)
- Department of Chemistry, University of Cambridge
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- Pawar, Amol P (author)
- Department of Chemistry, University of Cambridge
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- Watson, Ian E (author)
- Department of Chemistry, University of Cambridge
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- Chiti, Fabrizio (author)
- Dipartimento di Scienze Biochimiche, Università degli Studi di Firenze
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- Vendruscolo, Michele (author)
- Department of Chemistry, University of Cambridge
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- Lomas, David A (author)
- Department of Medicine, University of Cambridge
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- Dobson, Christopher M (author)
- Department of Chemistry, University of Cambridge
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- Crowther, Damian C (author)
- Department of Genetics, University of Cambridge, Cambridge
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(creator_code:org_t)
- 2007-10-30
- 2007
- English.
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In: PLoS biology. - : Public Library of Science (PLoS). - 1545-7885. ; 5:11, s. e290-
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Abstract
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- Protein aggregation into amyloid fibrils and protofibrillar aggregates is associated with a number of the most common neurodegenerative diseases. We have established, using a computational approach, that knowledge of the primary sequences of proteins is sufficient to predict their in vitro aggregation propensities. Here we demonstrate, using rational mutagenesis of the Abeta42 peptide based on such computational predictions of aggregation propensity, the existence of a strong correlation between the propensity of Abeta42 to form protofibrils and its effect on neuronal dysfunction and degeneration in a Drosophila model of Alzheimer disease. Our findings provide a quantitative description of the molecular basis for the pathogenicity of Abeta and link directly and systematically the intrinsic properties of biomolecules, predicted in silico and confirmed in vitro, to pathogenic events taking place in a living organism.
Keyword
- NATURAL SCIENCES
- NATURVETENSKAP
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Luheshi, Leila M
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Tartaglia, Gian ...
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Brorsson, Ann-Ch ...
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Pawar, Amol P
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Watson, Ian E
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Chiti, Fabrizio
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show more...
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Vendruscolo, Mic ...
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Lomas, David A
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Dobson, Christop ...
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Crowther, Damian ...
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- Articles in the publication
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PLoS biology
- By the university
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Linköping University