Frontiers in Aging Neuroscience (Mar 2021)
Doxycycline Interferes With Tau Aggregation and Reduces Its Neuronal Toxicity
- Luciana Medina,
- Florencia González-Lizárraga,
- Antonio Dominguez-Meijide,
- Antonio Dominguez-Meijide,
- Antonio Dominguez-Meijide,
- Diego Ploper,
- Valeria Parrales,
- Sabrina Sequeira,
- Maria-Sol Cima-Omori,
- Markus Zweckstetter,
- Markus Zweckstetter,
- Elaine Del Bel,
- Patrick P. Michel,
- Tiago Fleming Outeiro,
- Tiago Fleming Outeiro,
- Tiago Fleming Outeiro,
- Rita Raisman-Vozari,
- Rosana Chehín,
- Sergio B. Socias
Affiliations
- Luciana Medina
- Instituto de Investigación en Medicina Molecular y Celular Aplicada (IMMCA) (UNT-CONICET-SIPROSA), Tucumán, Argentina
- Florencia González-Lizárraga
- Instituto de Investigación en Medicina Molecular y Celular Aplicada (IMMCA) (UNT-CONICET-SIPROSA), Tucumán, Argentina
- Antonio Dominguez-Meijide
- Department of Experimental Neurodegeneration, Center for Biostructural Imaging of Neurodegeneration, University Medical Center Goettingen, Goettingen, Germany
- Antonio Dominguez-Meijide
- Laboratory of Neuroanatomy and Experimental Neurology, Department of Morphological Sciences, Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), University of Santiago de Compostela, Santiago de Compostela, Spain
- Antonio Dominguez-Meijide
- Networking Research Center on Neurodegenerative Diseases (CIBERNED), Madrid, Spain
- Diego Ploper
- Instituto de Investigación en Medicina Molecular y Celular Aplicada (IMMCA) (UNT-CONICET-SIPROSA), Tucumán, Argentina
- Valeria Parrales
- Sorbonne Université, Paris Brain Institute -ICM, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS), Assistance Publique - Hôpitaux de Paris (APHP), Hôpital de la Pitié Salpêtrière, Paris, France
- Sabrina Sequeira
- Instituto de Investigación en Medicina Molecular y Celular Aplicada (IMMCA) (UNT-CONICET-SIPROSA), Tucumán, Argentina
- Maria-Sol Cima-Omori
- German Center for Neurodegenerative Diseases Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Göttingen, Germany
- Markus Zweckstetter
- German Center for Neurodegenerative Diseases Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Göttingen, Germany
- Markus Zweckstetter
- Department for NMR-based Structural Biology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
- Elaine Del Bel
- Physiology- Dental School of Ribeirão Preto, University of São Paulo, São Paulo, Brazil
- Patrick P. Michel
- Sorbonne Université, Paris Brain Institute -ICM, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS), Assistance Publique - Hôpitaux de Paris (APHP), Hôpital de la Pitié Salpêtrière, Paris, France
- Tiago Fleming Outeiro
- Department of Experimental Neurodegeneration, Center for Biostructural Imaging of Neurodegeneration, University Medical Center Goettingen, Goettingen, Germany
- Tiago Fleming Outeiro
- Max Planck Institute for Experimental Medicine, Goettingen, Germany
- Tiago Fleming Outeiro
- 0Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom
- Rita Raisman-Vozari
- Sorbonne Université, Paris Brain Institute -ICM, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS), Assistance Publique - Hôpitaux de Paris (APHP), Hôpital de la Pitié Salpêtrière, Paris, France
- Rosana Chehín
- Instituto de Investigación en Medicina Molecular y Celular Aplicada (IMMCA) (UNT-CONICET-SIPROSA), Tucumán, Argentina
- Sergio B. Socias
- Instituto de Investigación en Medicina Molecular y Celular Aplicada (IMMCA) (UNT-CONICET-SIPROSA), Tucumán, Argentina
- DOI
- https://doi.org/10.3389/fnagi.2021.635760
- Journal volume & issue
-
Vol. 13
Abstract
Tauopathies are neurodegenerative disorders with increasing incidence and still without cure. The extensive time required for development and approval of novel therapeutics highlights the need for testing and repurposing known safe molecules. Since doxycycline impacts α-synuclein aggregation and toxicity, herein we tested its effect on tau. We found that doxycycline reduces amyloid aggregation of the 2N4R and K18 isoforms of tau protein in a dose-dependent manner. Furthermore, in a cell free system doxycycline also prevents tau seeding and in cell culture reduces toxicity of tau aggregates. Overall, our results expand the spectrum of action of doxycycline against aggregation-prone proteins, opening novel perspectives for its repurposing as a disease-modifying drug for tauopathies.
Keywords
