New Tacrine Dimers Alleviate the Intracellular Amyloid-β-induced Cognitive Disturbance and Oxidative Stress in Mice

This study aimed to investigate <italic>in vivo</italic> and <italic>ex-vivo</italic> the effects of tacrine dimers (TD1, TD2, TD3 and TD4) in mice with Alzheimer's disease (AD) induced by amyloid peptide (A<italic>β</italic>42) and, respectively, evaluated i...

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Detalhes bibliográficos
Autores: Gonçalves, Ana Elisa, Spigariol, Otto, Da Silva, Luísa M., Rego, Yuri F., Herrera-Arozamena, Clara, Rodríguez-Franco, María Isabel, De Fátima, Ângelo, Doring, Thiago Henrique, Araujo, Lucas Augusto, Macedo, Maria Lígia R, Saba, Sumbal, Rafique, Jamal, De Oliveira, Aldo S., De Souza, Márcia Maria
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/398782
Acesso em linha:http://hdl.handle.net/10261/398782
https://api.elsevier.com/content/abstract/scopus_id/105012571778
Access Level:acceso abierto
Palavra-chave:Amyloid-β (Aβ42)
Cognitive Disturbance
Neuroprotection
Oxidative Stress
Tacrine Dimers
Descrição
Resumo:This study aimed to investigate <italic>in vivo</italic> and <italic>ex-vivo</italic> the effects of tacrine dimers (TD1, TD2, TD3 and TD4) in mice with Alzheimer's disease (AD) induced by amyloid peptide (A<italic>β</italic>42) and, respectively, evaluated in behavioral tests of cognition, oxidative stress and neuroinflammation. All dimers reduced the cognitive deficit caused by A<italic>β</italic>42, oxidative stress and neuroinflammation, especially the compound TD4. By ADMET analysis (SwissADME and pkCSM 2.10 platforms), TD4 exhibited favorable pharmacokinetic properties with the control drug. The results suggest a therapeutic potential for AD for these compounds, given their distinct cognitive and neuroprotective effects in AD models induced by A<italic>β</italic>42.