دورية أكاديمية
Dynamics of oligomer populations formed during the aggregation of Alzheimer's Aβ42 peptide.
| العنوان: | Dynamics of oligomer populations formed during the aggregation of Alzheimer's Aβ42 peptide. |
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| المؤلفون: | Michaels TCT; Centre for Misfolding Diseases, Department of Chemistry, University of Cambridge, Cambridge, UK.; Paulson School of Engineering and Applied Science, Harvard University, Cambridge, MA, USA., Šarić A; Department of Physics and Astronomy, Institute for the Physics of Living Systems, University College London, London, UK.; MRC Laboratory for Molecular Cell Biology, University College London, London, UK., Curk S; Department of Physics and Astronomy, Institute for the Physics of Living Systems, University College London, London, UK.; MRC Laboratory for Molecular Cell Biology, University College London, London, UK.; Faculty of Natural Sciences and Mathematics, University of Maribor, Maribor, Slovenia., Bernfur K; Department of Chemistry, Division for Biochemistry and Structural Biology, Lund University, Lund, Sweden., Arosio P; Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland., Meisl G; Centre for Misfolding Diseases, Department of Chemistry, University of Cambridge, Cambridge, UK., Dear AJ; Centre for Misfolding Diseases, Department of Chemistry, University of Cambridge, Cambridge, UK.; Paulson School of Engineering and Applied Science, Harvard University, Cambridge, MA, USA., Cohen SIA; Centre for Misfolding Diseases, Department of Chemistry, University of Cambridge, Cambridge, UK., Dobson CM; Centre for Misfolding Diseases, Department of Chemistry, University of Cambridge, Cambridge, UK., Vendruscolo M; Centre for Misfolding Diseases, Department of Chemistry, University of Cambridge, Cambridge, UK. mv245@cam.ac.uk., Linse S; Department of Chemistry, Division for Biochemistry and Structural Biology, Lund University, Lund, Sweden. Sara.Linse@biochemistry.lu.se., Knowles TPJ; Centre for Misfolding Diseases, Department of Chemistry, University of Cambridge, Cambridge, UK. tpjk2@cam.ac.uk.; Cavendish Laboratory, University of Cambridge, Cambridge, UK. tpjk2@cam.ac.uk. |
| المصدر: | Nature chemistry [Nat Chem] 2020 May; Vol. 12 (5), pp. 445-451. Date of Electronic Publication: 2020 Apr 13. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101499734 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1755-4349 (Electronic) Linking ISSN: 17554330 NLM ISO Abbreviation: Nat Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: London : Nature Pub. Group |
| مواضيع طبية MeSH: | Alzheimer Disease/*metabolism , Amyloid beta-Peptides/*metabolism , Peptide Fragments/*metabolism, Computer Simulation ; Humans ; Kinetics ; Models, Molecular ; Peptide Fragments/chemistry ; Protein Conformation ; Protein Folding ; Protein Multimerization |
| مستخلص: | Oligomeric species populated during the aggregation of the Aβ42 peptide have been identified as potent cytotoxins linked to Alzheimer's disease, but the fundamental molecular pathways that control their dynamics have yet to be elucidated. By developing a general approach that combines theory, experiment and simulation, we reveal, in molecular detail, the mechanisms of Aβ42 oligomer dynamics during amyloid fibril formation. Even though all mature amyloid fibrils must originate as oligomers, we found that most Aβ42 oligomers dissociate into their monomeric precursors without forming new fibrils. Only a minority of oligomers converts into fibrillar structures. Moreover, the heterogeneous ensemble of oligomeric species interconverts on timescales comparable to those of aggregation. Our results identify fundamentally new steps that could be targeted by therapeutic interventions designed to combat protein misfolding diseases. |
| التعليقات: | Erratum in: Nat Chem. 2020 Apr 17;:. (PMID: 32303714) |
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| معلومات مُعتمدة: | United Kingdom BB_ Biotechnology and Biological Sciences Research Council |
| المشرفين على المادة: | 0 (Amyloid beta-Peptides) 0 (Peptide Fragments) 0 (amyloid beta-protein (1-42)) |
| تواريخ الأحداث: | Date Created: 20200415 Date Completed: 20201217 Latest Revision: 20210302 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1038/s41557-020-0452-1 |
| PMID: | 32284577 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1755-4349 |
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| DOI: | 10.1038/s41557-020-0452-1 |