Doxycycline Interferes With tau Aggregation and Reduces Its Neuronal Toxicity

MEDINA L.; GONZALES LIZARRAGA, MF; DOMINGUEZ-MEIJIDE A.; PLOPER D.; PARRALES V.; SEQUEIRA S.; CIMA-OMORRI M.; ZWECKSTETTER M; DEL-BEL, E.; MICHEL, P.; OUTEIRO T; RAISMAN VOZARI R.; CHEHÍN R.; SOCIAS SB.

Frontiers in Aging Neuroscience

Frontiers Media S.A.

Año: 2021

1663-4365

Tauopathies are neurodegenerative disorders with increasing incidence and still withoutcure. The extensive time required for development and approval of novel therapeuticshighlights the need for testing and repurposing known safe molecules. Since doxycyclineimpacts a-synuclein aggregation and toxicity, herein we tested its effect on tau. Wefound that doxycycline reduces amyloid aggregation of the 2N4R and K18 isoforms oftau protein in a dose-dependent manner. Furthermore, in a cell free system doxycyclinealso prevents tau seeding and in cell culture reduces toxicity of tau aggregates. Overall,our results expand the spectrum of action of doxycycline against aggregation-proneproteins, opening novel perspectives for its repurposing as a disease-modifying drugfor tauopathies.