Inhibition of α-synuclein phosphorylation, seeding and lysosomal stress by DCT, a non-antibiotic chlorinated tetracycline

RAISMAN VOZARI, R; GUAYAN, ML; TOMAS GRAU, RH; FIGADÈRE, B; ROSE, CLÉMENCE; SALADO, C; CHEHÍN, R; PLOPER, D

Lisbon

Conferencia; AD/PD? 2024 International Conference on Alzheimer?s and Parkinson?s Diseases and related neurological disorders; 2024

Parkinson's Disease is a chronic and progressive neurodegenerative disorder that affects millions worldwide. This condition is characterized by the presence oftoxic amyloid aggregates of the α-synuclein protein (αS), predominantly phosphorylated at Serine 129. So far, only symptomatic treatments exist.Previously, it was demonstrated that different tetracyclines (TCs) possess neuroprotective properties in preclinical models. However, their antibiotic activityprevents their repurposing. Therefore, through rational drug design, different TCs devoid of antibiotic activity were developed.The objective of this project is to evaluate the potential of DCT, one of these chemically modified TCs, as a neuroprotective molecule using a commerciallyavailable transgenic cell line that overexpresses a fluorescently tagged αS.