C9-FUNCTIONALIZED DOXYCYCLINE ANALOGS: A PROMISING APPROACH AGAINST α-SYNUCLEIN AGGREGATION AND LPS-INDUCED NEUROINFLAMMATION

RAISMAN VOZARI, R; TOMAS GRAU, RH; ROSE, CLÉMENCE; ZABALA, BRENDA; MICHEL, PATRICK P.; BRUNEL, JM; CHEHÍN, R; FERRIE, L; FIGADÈRE, B

Lisbon

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

Doxycycline (DOX), a member of the tetracycline family, exhibits several properties,including antibiotic, antifungal, and antineoplastic effects. It has been demonstratedneuroprotective effects in experimental Parkinson's disease (PD) models, includinginhibition of α-synuclein (α-Syn) aggregation, reduction of oxidative stress, and suppression of neuro-inflammation. Despite its potential for neuroprotection in PD and other neurodegenerative diseases, prolonged use raises concerns about antibiotic resistance and microbiota disruption. In the exploration of non-antibiotic alternatives, we synthesized eighteen DOX derivatives, two of which demonstrated improved efficacy at inhibiting α-Syn aggregation and mitigating neuro-inflammation compared to DOX, in a primary microglial cell cultures.