AUTHOR=Medina Luciana , González-Lizárraga Florencia , Dominguez-Meijide Antonio , Ploper Diego , Parrales Valeria , Sequeira Sabrina , Cima-Omori Maria-Sol , Zweckstetter Markus , Del Bel Elaine , Michel Patrick P. , Outeiro Tiago Fleming , Raisman-Vozari Rita , Chehín Rosana , Socias Sergio B. TITLE=Doxycycline Interferes With Tau Aggregation and Reduces Its Neuronal Toxicity JOURNAL=Frontiers in Aging Neuroscience VOLUME=13 YEAR=2021 URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2021.635760 DOI=10.3389/fnagi.2021.635760 ISSN=1663-4365 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.