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.
P#223
Doxycycline modifies tau fibrillization and reduces its toxicity
Luciana Medina
- San Miguel de Tucumán,
- Argentina
- Luciana Medina ¹
- , María Florencia González Lizárraga ¹
- , Sabrina Sequeira ¹
- , Rita Raisman-Vozari ³
- , Sergio Benjamín Socías ¹
- , Rosana Nieves Chehín ¹
- 1 IMMCA Instituto de Investigación en Medicina Molecular y Celular Aplicada (CONICET - UNT – SIPROSA), Tucumán, Argentina
- 2 INSIBIO Instituto Superior de Investigaciones Biológicas (CONICET-UNT), Tucumán, Argentina
- 3 ICM - Institut du Cerveau et de la Moelle Epinière - Hôpital Pitié Salpêtrière , Paris, France