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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
28-29
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pubmed:dateCreated |
2006-12-4
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pubmed:abstractText |
The formation of fibrils by amyloid beta-protein (Abeta) is considered as a key step in the pathology of Alzheimer's disease (AD). Inhibiting the aggregation of Abeta is a promising approach for AD therapy. In this study, we used biocompatible nanogels composed of a polysaccharide pullulan backbone with hydrophobic cholesterol moieties (cholesterol-bearing pullulan, CHP) as artificial chaperones to inhibit the formation of Abeta-(1-42) fibrils with marked amyloidgenic activity and cytotoxicity. The CHP-nanogels incorporated up to 6-8 Abeta-(1-42) molecules per particle and induced a change in the conformation of Abeta from a random coil to alpha-helix- or beta-sheet-rich structure. This structure was stable even after a 24-h incubation at 37 degrees C and the aggregation of Abeta-(1-42) was suppressed. Furthermore, the dissociation of the nanogels caused by the addition of methyl-beta-cyclodextrin released monomeric Abeta molecules. Nanogels composed of amino-group-modified CHP (CHPNH(2)) with positive charges under physiological conditions had a greater inhibitory effect than CHP-nanogels, suggesting the importance of electrostatic interactions between CHPNH(2) and Abeta for inhibiting the formation of fibrils. In addition, CHPNH(2) nanogels protected PC12 cells from Abeta toxicity.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/7-diethylaminocoumarin-3-carboxylic...,
http://linkedlifedata.com/resource/pubmed/chemical/Amyloid beta-Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Biocompatible Materials,
http://linkedlifedata.com/resource/pubmed/chemical/Cholesterol,
http://linkedlifedata.com/resource/pubmed/chemical/Coumarins,
http://linkedlifedata.com/resource/pubmed/chemical/Glucans,
http://linkedlifedata.com/resource/pubmed/chemical/Molecular Chaperones,
http://linkedlifedata.com/resource/pubmed/chemical/NanoGel,
http://linkedlifedata.com/resource/pubmed/chemical/Polyethylene Glycols,
http://linkedlifedata.com/resource/pubmed/chemical/Polyethyleneimine,
http://linkedlifedata.com/resource/pubmed/chemical/pullulan
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0014-5793
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
11
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pubmed:volume |
580
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6587-95
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:17125770-Amyloid beta-Peptides,
pubmed-meshheading:17125770-Animals,
pubmed-meshheading:17125770-Biocompatible Materials,
pubmed-meshheading:17125770-Cell Death,
pubmed-meshheading:17125770-Cholesterol,
pubmed-meshheading:17125770-Chromatography, Gel,
pubmed-meshheading:17125770-Circular Dichroism,
pubmed-meshheading:17125770-Coumarins,
pubmed-meshheading:17125770-Glucans,
pubmed-meshheading:17125770-Humans,
pubmed-meshheading:17125770-Microscopy, Electron, Transmission,
pubmed-meshheading:17125770-Models, Biological,
pubmed-meshheading:17125770-Molecular Chaperones,
pubmed-meshheading:17125770-Neurofibrils,
pubmed-meshheading:17125770-PC12 Cells,
pubmed-meshheading:17125770-Polyethylene Glycols,
pubmed-meshheading:17125770-Polyethyleneimine,
pubmed-meshheading:17125770-Protein Structure, Quaternary,
pubmed-meshheading:17125770-Protein Structure, Secondary,
pubmed-meshheading:17125770-Rats,
pubmed-meshheading:17125770-Spectrometry, Fluorescence,
pubmed-meshheading:17125770-Temperature
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pubmed:year |
2006
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pubmed:articleTitle |
Inhibition of the formation of amyloid beta-protein fibrils using biocompatible nanogels as artificial chaperones.
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pubmed:affiliation |
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, 606-8501, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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