Fast fluorescence lifetime imaging reveals the aggregation processes of α-synuclein and polyglutamine in aging Caenorhabditis elegans
| العنوان: | Fast fluorescence lifetime imaging reveals the aggregation processes of α-synuclein and polyglutamine in aging Caenorhabditis elegans |
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| المؤلفون: | Amanda J. Haack, Peter Gaida, Tessa Sinnige, Michele Vendruscolo, Nathan Curry, Kai Yu Ma, Clemens F. Kaminski, Romain F. Laine, Michele Perni, Christopher M. Dobson, Chetan Poudel, Gabriele S. Kaminski Schierle, Ellen A. A. Nollen |
| المساهمون: | Laine, Romain F [0000-0002-2151-4487], Sinnige, Tessa [0000-0002-9353-126X], Poudel, Chetan [0000-0002-8512-9238], Perni, Michele [0000-0001-7593-8376], Vendruscolo, Michele [0000-0002-3616-1610], Kaminski Schierle, Gabriele S [0000-0002-1843-2202], Kaminski, Clemens F [0000-0002-5194-0962], Apollo - University of Cambridge Repository, Molecular Neuroscience and Ageing Research (MOLAR) |
| المصدر: | ACS Chem Biol ACS Chemical Biology ACS chemical biology, 14(7), 1628-1636. AMER CHEMICAL SOC |
| بيانات النشر: | Cold Spring Harbor Laboratory, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Aging, Amyloid, Fluorescence-lifetime imaging microscopy, Huntingtin, ved/biology.organism_classification_rank.species, PROTEIN, Protein aggregation, 01 natural sciences, Biochemistry, DISEASE, Article, Protein Aggregates, 03 medical and health sciences, HUNTINGTIN, 0302 clinical medicine, In vivo, Animals, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Model organism, 030304 developmental biology, 0303 health sciences, biology, 010405 organic chemistry, ved/biology, Chemistry, Optical Imaging, General Medicine, IN-VITRO, biology.organism_classification, In vitro, 0104 chemical sciences, Cell biology, Functional imaging, 030104 developmental biology, AMYLOID FORMATION, alpha-Synuclein, Molecular Medicine, α synuclein, Peptides, 030217 neurology & neurosurgery |
| الوصف: | The nematode worm Caenorhabditis elegans has emerged as an important model organism to study the molecular mechanisms of protein misfolding diseases associated with amyloid formation because of its small size, ease of genetic manipulation and optical transparency. Obtaining a reliable and quantitative read-out of protein aggregation in this system, however, remains a challenge. To address this problem, we here present a fast time-gated fluorescence lifetime imaging (TG-FLIM) method and show that it provides functional insights into the process of protein aggregation in living animals by enabling the rapid characterisation of different types of aggregates. More specifically, in longitudinal studies of C. elegans models of Parkinson’s and Huntington’s diseases, we observed marked differences in the aggregation kinetics and the nature of the protein inclusions formed by α-synuclein and polyglutamine. In particular, we found that α-synuclein inclusions do not display amyloid-like features until late in the life of the worms, whereas polyglutamine forms amyloid characteristics rapidly in early adulthood. Furthermore, we show that the TG-FLIM method is capable of imaging live and non-anaesthetised worms moving in specially designed agarose micro-chambers. Taken together, our results show that the TG-FLIM method enables high-throughput functional imaging of living C. elegans that can be used to study in vivo mechanisms of aggregation and that has the potential to aid the search for therapeutic modifiers of protein aggregation and toxicity. |
| وصف الملف: | application/pdf |
| تدمد: | 1554-8929 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9b08c9aeb079f22e82b3e9604b7fca3d https://doi.org/10.1101/414714 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....9b08c9aeb079f22e82b3e9604b7fca3d |
| قاعدة البيانات: | OpenAIRE |
Find this issue from the American Chemical Society | تدمد: | 15548929 |
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