The Molecular Chaperone Artemin Efficiently Blocks Fibrillization of TAU Protein In Vitro
Journal Title: Cell Journal(Yakhteh) - Year 2018, Vol 19, Issue 4
Abstract
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.
Authors and Affiliations
Zahra Khosravi Anbaran, Mohammad Ali Nasiri Khalili et al. , Sharif Moradi, Reza Hassan Sajedi, Mehdi Zeinoddini
Keywords
Related Articles
- EP ID EP532385
- DOI 10.22074/cellj.2018.4510
- Views 192
- Downloads 0
Repression of TGF-β Signaling in Breast Cancer Cells by miR-302/367 Cluster
Objective: Epigenetic alterations of the malignantly transformed cells have increasingly been regarded as an important event in the carcinogenic development. Induction of some miRNAs such as miR-302/367 cluster has been...
VDR and CYP24A1 Expression Analysis in Iranian Relapsing-Remitting Multiple Sclerosis Patients
Objective: Multiple sclerosis (MS) is a common disease of the central nervous system. This disease may be initiated by either vitamin deficiency or triggered by abnormality in CYP24A1 and vitamin D receptor. Materials an...
Stochastic Cell Fate and Longevity of Offspring
Objective: Cellular decision-making is a key process in which cells with similar genetic and environmental background make dissimilar decisions. This stochastic process, which happens in prokaryotic and eukaryotic cells...
Ameliorating Effect of Ginseng on Epididymo-Orchitis Inducing Alterations in Sperm Quality and Spermatogenic Cells Apoptosis following Infection by Uropathogenic Escherichia coli in Rats
Objective Epididymo-orchitis (EO) potentially results in reduced fertility in up to 60% of affected patients. The anti-inflammatory effects of Korean red ginseng (KRG) and its ability to act as an immunoenhancer in paral...
Anacardic Acid Reduces Acetylation of H4K12 in Mouse Oocytes during Vitrification
Objective: Over the last years, vitrification has been widely used for oocyte cryopreservation, in animals and humans; however, it frequently causes minor and major epigenetic modifications. The effect of oocyte vitrific...