دورية أكاديمية
أعرض في EDS

In situ kinetic measurements of α-synuclein aggregation reveal large population of short-lived oligomers.

التفاصيل البيبلوغرافية
العنوان: In situ kinetic measurements of α-synuclein aggregation reveal large population of short-lived oligomers.
المؤلفون: Zurlo E; Department of Physics, Huygens-Kamerlingh Onnes Laboratory, Leiden University, Leiden, The Netherlands., Kumar P; Department of Physics, Huygens-Kamerlingh Onnes Laboratory, Leiden University, Leiden, The Netherlands., Meisl G; Centre for Misfolding Diseases, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, United Kingdom., Dear AJ; Centre for Misfolding Diseases, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, United Kingdom., Mondal D; Department of Physics, Huygens-Kamerlingh Onnes Laboratory, Leiden University, Leiden, The Netherlands., Claessens MMAE; Nanobiophysics Group, Department of Science and Technology, University Twente, Enschede, The Netherlands., Knowles TPJ; Centre for Misfolding Diseases, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, United Kingdom.; Cavendish Laboratory, University of Cambridge, Cambridge, United Kingdom., Huber M; Department of Physics, Huygens-Kamerlingh Onnes Laboratory, Leiden University, Leiden, The Netherlands.
المصدر: PloS one [PLoS One] 2021 Jan 22; Vol. 16 (1), pp. e0245548. Date of Electronic Publication: 2021 Jan 22 (Print Publication: 2021).
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science
مواضيع طبية MeSH: Protein Aggregates* , Protein Multimerization*, alpha-Synuclein/*chemistry, Kinetics ; Protein Structure, Quaternary
مستخلص: Knowledge of the mechanisms of assembly of amyloid proteins into aggregates is of central importance in building an understanding of neurodegenerative disease. Given that oligomeric intermediates formed during the aggregation reaction are believed to be the major toxic species, methods to track such intermediates are clearly needed. Here we present a method, electron paramagnetic resonance (EPR), by which the amount of intermediates can be measured over the course of the aggregation, directly in the reacting solution, without the need for separation. We use this approach to investigate the aggregation of α-synuclein (αS), a synaptic protein implicated in Parkinson's disease and find a large population of oligomeric species. Our results show that these are primary oligomers, formed directly from monomeric species, rather than oligomers formed by secondary nucleation processes, and that they are short-lived, the majority of them dissociates rather than converts to fibrils. As demonstrated here, EPR offers the means to detect such short-lived intermediate species directly in situ. As it relies only on the change in size of the detected species, it will be applicable to a wide range of self-assembling systems, making accessible the kinetics of intermediates and thus allowing the determination of their rates of formation and conversion, key processes in the self-assembly reaction.
Competing Interests: The authors have declared that no competing interests exist.
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المشرفين على المادة: 0 (Protein Aggregates)
0 (alpha-Synuclein)
تواريخ الأحداث: Date Created: 20210122 Date Completed: 20210611 Latest Revision: 20210611
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC7822277
DOI: 10.1371/journal.pone.0245548
PMID: 33481908
قاعدة البيانات: MEDLINE
الوصف
تدمد:1932-6203
DOI:10.1371/journal.pone.0245548