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

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

Abstract 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, evaluat...

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Main Authors: ANA ELISA GONÇALVES, OTTO SPIGARIOL, LUÍSA M. DA SILVA, YURI F. REGO, CLARA HERRERA-AROZAMENA, MARÍA ISABEL RODRÍGUEZ-FRANCO, ÂNGELO DE FÁTIMA, THIAGO HENRIQUE DORING, LUCAS AUGUSTO ARAUJO, MARIA LÍGIA R. MACEDO, SUMBAL SABA, JAMAL RAFIQUE, ALDO S. DE OLIVEIRA, MÁRCIA MARIA DE SOUZA
Format: Article
Language:English
Published: Academia Brasileira de Ciências 2025-07-01
Series:Anais da Academia Brasileira de Ciências
Subjects:
Tacrine Dimers
Amyloid-β (Aβ42)
Cognitive Disturbance
Oxidative Stress
Neuroprotection
Online Access:http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0001-37652025001100601&lng=en&tlng=en
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Summary:Abstract 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.
ISSN:1678-2690

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