The extracellular chaperone clusterin sequesters oligomeric forms of the amyloid-β(1-40) peptide.
Identifieur interne : 000908 ( Ncbi/Curation ); précédent : 000907; suivant : 000909The extracellular chaperone clusterin sequesters oligomeric forms of the amyloid-β(1-40) peptide.
Auteurs : Priyanka Narayan [Royaume-Uni] ; Angel Orte ; Richard W. Clarke ; Benedetta Bolognesi ; Sharon Hook ; Kristina A. Ganzinger ; Sarah Meehan ; Mark R. Wilson ; Christopher M. Dobson ; David KlenermanSource :
- Nature structural & molecular biology [ 1545-9985 ] ; 2011.
Descripteurs français
- KwdFr :
- Algorithmes, Amyloïde (), Amyloïde (métabolisme), Amyloïde (ultrastructure), Chaperons moléculaires (), Chaperons moléculaires (métabolisme), Cinétique, Clusterine (), Clusterine (métabolisme), Espace extracellulaire (métabolisme), Fluorescence, Fluorimétrie (), Fluorimétrie (instrumentation), Fragments peptidiques (), Fragments peptidiques (métabolisme), Humains, Liaison aux protéines, Maladie d'Alzheimer (métabolisme), Microscopie confocale, Microscopie électronique à transmission, Multimérisation de protéines, Peptides bêta-amyloïdes (), Peptides bêta-amyloïdes (métabolisme), Thermodynamique.
- MESH :
- métabolisme : Amyloïde, Chaperons moléculaires, Clusterine, Espace extracellulaire, Fragments peptidiques, Maladie d'Alzheimer, Peptides bêta-amyloïdes.
- Algorithmes, Amyloïde, Chaperons moléculaires, Cinétique, Clusterine, Fluorescence, Fluorimétrie, Fragments peptidiques, Humains, Liaison aux protéines, Microscopie confocale, Microscopie électronique à transmission, Multimérisation de protéines, Peptides bêta-amyloïdes, Thermodynamique.
English descriptors
- KwdEn :
- Algorithms, Alzheimer Disease (metabolism), Amyloid (chemistry), Amyloid (metabolism), Amyloid (ultrastructure), Amyloid beta-Peptides (chemistry), Amyloid beta-Peptides (metabolism), Clusterin (chemistry), Clusterin (metabolism), Extracellular Space (metabolism), Fluorescence, Fluorometry (instrumentation), Fluorometry (methods), Humans, Kinetics, Microscopy, Confocal, Microscopy, Electron, Transmission, Molecular Chaperones (chemistry), Molecular Chaperones (metabolism), Peptide Fragments (chemistry), Peptide Fragments (metabolism), Protein Binding, Protein Multimerization, Thermodynamics.
- MESH :
- chemical , chemistry : Amyloid, Amyloid beta-Peptides, Clusterin, Molecular Chaperones, Peptide Fragments.
- instrumentation : Fluorometry.
- metabolism : Alzheimer Disease, Amyloid, Amyloid beta-Peptides, Clusterin, Extracellular Space, Molecular Chaperones, Peptide Fragments.
- methods : Fluorometry.
- chemical , ultrastructure : Amyloid.
- Algorithms, Fluorescence, Humans, Kinetics, Microscopy, Confocal, Microscopy, Electron, Transmission, Protein Binding, Protein Multimerization, Thermodynamics.
Abstract
In recent genome-wide association studies, the extracellular chaperone protein, clusterin, has been identified as a newly-discovered risk factor in Alzheimer's disease. We have examined the interactions between human clusterin and the Alzheimer's disease-associated amyloid-β(1-40) peptide (Aβ(1-40)), which is prone to aggregate into an ensemble of oligomeric intermediates implicated in both the proliferation of amyloid fibrils and in neuronal toxicity. Using highly sensitive single-molecule fluorescence methods, we have found that Aβ(1-40) forms a heterogeneous distribution of small oligomers (from dimers to 50-mers), all of which interact with clusterin to form long-lived, stable complexes. Consequently, clusterin is able to influence both the aggregation and disaggregation of Aβ(1-40) by sequestration of the Aβ oligomers. These results not only elucidate the protective role of clusterin but also provide a molecular basis for the genetic link between clusterin and Alzheimer's disease.
DOI: 10.1038/nsmb.2191
PubMed: 22179788
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Dobson</name></author><author><name sortKey="Klenerman, David" sort="Klenerman, David" uniqKey="Klenerman D" first="David" last="Klenerman">David Klenerman</name></author></analytic><series><title level="j">Nature structural & molecular biology</title><idno type="eISSN">1545-9985</idno><imprint><date when="2011" type="published">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Algorithms</term><term>Alzheimer Disease (metabolism)</term><term>Amyloid (chemistry)</term><term>Amyloid (metabolism)</term><term>Amyloid (ultrastructure)</term><term>Amyloid beta-Peptides (chemistry)</term><term>Amyloid beta-Peptides (metabolism)</term><term>Clusterin (chemistry)</term><term>Clusterin (metabolism)</term><term>Extracellular Space (metabolism)</term><term>Fluorescence</term><term>Fluorometry (instrumentation)</term><term>Fluorometry (methods)</term><term>Humans</term><term>Kinetics</term><term>Microscopy, Confocal</term><term>Microscopy, Electron, Transmission</term><term>Molecular Chaperones (chemistry)</term><term>Molecular Chaperones (metabolism)</term><term>Peptide Fragments (chemistry)</term><term>Peptide Fragments (metabolism)</term><term>Protein Binding</term><term>Protein Multimerization</term><term>Thermodynamics</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Algorithmes</term><term>Amyloïde ()</term><term>Amyloïde (métabolisme)</term><term>Amyloïde (ultrastructure)</term><term>Chaperons moléculaires ()</term><term>Chaperons moléculaires (métabolisme)</term><term>Cinétique</term><term>Clusterine ()</term><term>Clusterine (métabolisme)</term><term>Espace extracellulaire (métabolisme)</term><term>Fluorescence</term><term>Fluorimétrie ()</term><term>Fluorimétrie (instrumentation)</term><term>Fragments peptidiques ()</term><term>Fragments peptidiques (métabolisme)</term><term>Humains</term><term>Liaison aux protéines</term><term>Maladie d'Alzheimer (métabolisme)</term><term>Microscopie confocale</term><term>Microscopie électronique à transmission</term><term>Multimérisation de protéines</term><term>Peptides bêta-amyloïdes ()</term><term>Peptides bêta-amyloïdes (métabolisme)</term><term>Thermodynamique</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Amyloid</term><term>Amyloid beta-Peptides</term><term>Clusterin</term><term>Molecular Chaperones</term><term>Peptide Fragments</term></keywords><keywords scheme="MESH" qualifier="instrumentation" xml:lang="en"><term>Fluorometry</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Alzheimer Disease</term><term>Amyloid</term><term>Amyloid beta-Peptides</term><term>Clusterin</term><term>Extracellular Space</term><term>Molecular Chaperones</term><term>Peptide Fragments</term></keywords><keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Fluorometry</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Amyloïde</term><term>Chaperons moléculaires</term><term>Clusterine</term><term>Espace extracellulaire</term><term>Fragments peptidiques</term><term>Maladie d'Alzheimer</term><term>Peptides bêta-amyloïdes</term></keywords><keywords scheme="MESH" type="chemical" qualifier="ultrastructure" xml:lang="en"><term>Amyloid</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Algorithms</term><term>Fluorescence</term><term>Humans</term><term>Kinetics</term><term>Microscopy, Confocal</term><term>Microscopy, Electron, Transmission</term><term>Protein Binding</term><term>Protein Multimerization</term><term>Thermodynamics</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Algorithmes</term><term>Amyloïde</term><term>Chaperons moléculaires</term><term>Cinétique</term><term>Clusterine</term><term>Fluorescence</term><term>Fluorimétrie</term><term>Fragments peptidiques</term><term>Humains</term><term>Liaison aux protéines</term><term>Microscopie confocale</term><term>Microscopie électronique à transmission</term><term>Multimérisation de protéines</term><term>Peptides bêta-amyloïdes</term><term>Thermodynamique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">In recent genome-wide association studies, the extracellular chaperone protein, clusterin, has been identified as a newly-discovered risk factor in Alzheimer's disease. We have examined the interactions between human clusterin and the Alzheimer's disease-associated amyloid-β(1-40) peptide (Aβ(1-40)), which is prone to aggregate into an ensemble of oligomeric intermediates implicated in both the proliferation of amyloid fibrils and in neuronal toxicity. Using highly sensitive single-molecule fluorescence methods, we have found that Aβ(1-40) forms a heterogeneous distribution of small oligomers (from dimers to 50-mers), all of which interact with clusterin to form long-lived, stable complexes. Consequently, clusterin is able to influence both the aggregation and disaggregation of Aβ(1-40) by sequestration of the Aβ oligomers. These results not only elucidate the protective role of clusterin but also provide a molecular basis for the genetic link between clusterin and Alzheimer's disease.</div></front></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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