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A New Tacrine–Melatonin Hybrid Reduces Amyloid Burden and Behavioral Deficits in a Mouse Model of Alzheimer’s Disease

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Abstract

Alzheimer’s disease (AD) is a progressive degenerative disorder characterized by the presence of amyloid deposits, neurofibrillary tangles and neuron loss. Emerging evidence indicates that antioxidants could be useful either for the prevention or treatment of AD. Tacrine and melatonin are well-known drugs which act as an acetylcholinesterase inhibitor and a free radical scavenger, respectively. In this study, we evaluated the effects of a new tacrine–melatonin hybrid on behavior and the biochemical and neuropathologic changes observed in amyloid precursor protein/presenilin 1 (APP/Ps1) transgenic mice. Our findings showed that direct intracerebral administration of this hybrid decreased amyloid β peptide (Aβ)-induced cell death and amyloid burden in the brain parenchyma of APP/Ps1 mice. This reduction in Aβ pathology was accompanied by a recovery in cognitive function. Since this tacrine–melatonin hybrid apparently reduces brain Aβ and behavioral deficits, we believe this drug has remarkable and significant neuroprotective effects and might be considered a potential therapeutic strategy in AD.

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Acknowledgments

There is no conflict of interest with other people or organizations. This work was supported by grants from Fondo de Investigación Sanitaria (FIS) (CP04/00179, PI060155), Fundación Investigación Médica Mutua Madrileña (2006.125), CIBERNED, and Ministerio de Educación y Ciencia (BFU2006-07430/BFI and SAF2006-01249). We thank Dr. Washington Buño and Dr. David Fernandez de Sevilla for expert help in brain organotypic culture. We thank Dr. Ximena Alvira-Botero for editorial assistance.

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Authors and Affiliations

  1. Neuroscience Laboratory, University Hospital, 12 de Octubre Research Center, 28041, Madrid, Spain

    Carlos Spuch, Desiree Antequera & Eva Carro

  2. Neurodegenerative Diseases Biomedical Research Center (CIBERNED), Madrid, Spain

    Carlos Spuch, Desiree Antequera & Eva Carro

  3. Instituto de Química Médica (CSIC), Madrid, Spain

    M. Isabel Fernandez-Bachiller & M. Isabel Rodríguez-Franco

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  1. Carlos Spuch
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  2. Desiree Antequera
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  3. M. Isabel Fernandez-Bachiller
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  4. M. Isabel Rodríguez-Franco
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  5. Eva Carro
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Correspondence to Eva Carro.

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Spuch, C., Antequera, D., Isabel Fernandez-Bachiller, M. et al. A New Tacrine–Melatonin Hybrid Reduces Amyloid Burden and Behavioral Deficits in a Mouse Model of Alzheimer’s Disease. Neurotox Res 17, 421–431 (2010). https://doi.org/10.1007/s12640-009-9121-2

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