CMT-3 targets different α-synuclein aggregates mitigating their toxic and inflammogenic effects
- González Lizarraga, Maria Florencia
- Ploper, Diego
- Avila, Cesar Luis
- Socias, Sergio Benjamin
- dos Santos Pereira, Mauricio
- Machín, Belén
- Del Bel, Elaine
- Michel, Patrick Pierre
- Pietrasanta, Lia
- Raisman Vozari, Rita
- Chehin, Rosana Nieves
DOIAbstract
Parkinson's disease (PD) is a neurodegenerative disorder for which only symptomatic treatments are available. Repurposing drugs that target α-synuclein aggregation, considered one of the main drivers of PD progression, could accelerate the development of disease-modifying therapies. In this work, we focused on chemically modified tetracycline 3 (CMT-3), a derivative with reduced antibiotic activity that crosses the blood–brain barrier and is pharmacologically safe. We found that CMT-3 inhibited α-synuclein amyloid aggregation and led to the formation of non-toxic molecular species, unlike minocycline. Furthermore, CMT-3 disassembled preformed α-synuclein amyloid fibrils into smaller fragments that were unable to seed in subsequent aggregati...
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