SAN2020

Tauopathies are neurodegenerative diseases characterized by the aggregation of the microtubule associated protein tau, without a cure to date. The increasing incidence of these disorders, and the extensive time required for the development and approval of novel drugs, highlight the need for testing and repurposing known safe molecules for new indications. Using biophysical and biochemical techniques we investigated the effect of doxycycline, a member of the tetracycline antibiotic family, on tau amyloid aggregation and neurotoxicity. Doxycycline reduced tau fibrillization in a dose-dependent manner, and increased protease sensitivity of tau fibrils. Also, doxycycline blocked tau seeding and diminished the toxicity of tau aggregates in cell culture. Overall, our results expand the spectrum of action of doxycycline against aggregation-prone proteins, opening novel perspectives for its use as a disease modifying drug for tauopathies.