The Molecular Chaperone Artemin Efficiently Blocks Fibrillization of TAU Protein In Vitro
| Autor: | Zahra Khosravi, Mohammad Ali Nasiri Khalili, Sharif Moradi, Reza Hassan Sajedi, Mehdi Zeinoddini |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: | |
| Zdroj: | Cell Journal, Vol 19, Iss 4, Pp 569-577 (2017) |
| Druh dokumentu: | article |
| ISSN: | 2228-5806 2228-5814 59440619 |
| DOI: | 10.22074/cellj.2018.4510 |
| Popis: | Objective: Aggregation of the TAU proteins in the form of neurofibrillary tangles (NFTs) in the brain is a common risk factor in tauopathies including Alzheimer’s disease (AD). Several strategies have been implemented to target NFTs, among which chaperones, which facilitate the proper folding of proteins, appear to hold great promise in effectively inhibiting TAU polymerization. The aim of this study was to analyze the impact of the chaperone Artemin on TAU aggregation in vitro. Materials and Methods: In this experimental study, recombinant TAU- or Artemin proteins were expressed in E.coli bacteria, and purified using ion-exchange and affinity chromatography. Sodium dodecyl sulfate-poly acrylamide gel electrophoresis (SDS-PAGE) was used to run the extracted proteins and check their purity. Heparin was used as an aggregation inducer. The interaction kinetics of TAU aggregation and disassembly was performed using thioflavin T (ThT) fluorescence analysis and circular dichroism (CD) spectroscopy. Results: Ion-exchange and affinity chromatography yielded highly pure TAU and Artemin proteins for subsequent analyses. In addition, we found that heparin efficiently induced TAU fibrillization 48 hours post-incubation, as evidenced by ThT assay. Importantly, Artemin was observed to effectively block the aggregation of both physiologic- and supraphysiologic TAU concentrations in a dose-dependent manner, as judged by ThT and CD spectroscopy analyses. Conclusion: Our collective results show, for the first time, that the chaperone Artemin could significantly inhibit aggregation of the TAU proteins in a dose-dependent manner, and support Artemin as a potential potent blocker of TAU aggregation in people with AD. |
| Databáze: | Directory of Open Access Journals |
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