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Research Article

Pharmacological tools based on imidazole scaffold proved the utility of PDE10A inhibitors for Parkinson’s disease

    Ana M García‡

    Centro de Investigaciones Biológicas (CSIC), Ramiro de Maeztu 9, 28040 Madrid, Spain

    ‡Authors contributed equally

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    ,
    Irene G Salado‡

    Centro de Investigaciones Biológicas (CSIC), Ramiro de Maeztu 9, 28040 Madrid, Spain

    ‡Authors contributed equally

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    ,
    Daniel I Perez

    Centro de Investigaciones Biológicas (CSIC), Ramiro de Maeztu 9, 28040 Madrid, Spain

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    ,
    José Brea

    Instituto de Farmacia Industrial, Facultad de Farmacia, Universidad de Santiago de Compostela, Campus Universitario Sur s/n, 15782 Santiago de Compostela, Spain

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    ,
    Jose A Morales-García

    Instituto de Investigaciones Biomédicas (CSIC-UAM), Arturo Duperier 4, 28029 Madrid, Spain

    Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED)

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    ,
    Alejandro González-García

    Instituto de Farmacia Industrial, Facultad de Farmacia, Universidad de Santiago de Compostela, Campus Universitario Sur s/n, 15782 Santiago de Compostela, Spain

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    ,
    María Isabel Cadavid

    Instituto de Farmacia Industrial, Facultad de Farmacia, Universidad de Santiago de Compostela, Campus Universitario Sur s/n, 15782 Santiago de Compostela, Spain

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    ,
    María Isabel Loza

    Instituto de Farmacia Industrial, Facultad de Farmacia, Universidad de Santiago de Compostela, Campus Universitario Sur s/n, 15782 Santiago de Compostela, Spain

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    ,
    Francisco Javier Luque

    Facultad de Farmacia & Instituto de Biomedicina (IBUB), Universidad de Barcelona, Barcelona, Spain

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    ,
    Ana Perez-Castillo

    Instituto de Investigaciones Biomédicas (CSIC-UAM), Arturo Duperier 4, 28029 Madrid, Spain

    Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED)

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    ,
    Ana Martinez

    Centro de Investigaciones Biológicas (CSIC), Ramiro de Maeztu 9, 28040 Madrid, Spain

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    &
    Carmen Gil

    *Author for correspondence:

    E-mail Address: carmen.gil@csic.es

    Centro de Investigaciones Biológicas (CSIC), Ramiro de Maeztu 9, 28040 Madrid, Spain

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    Published Online:9 May 2017https://doi.org/10.4155/fmc-2017-0005

    Abstract

    Aim: Since neuroinflammation is partially mediated by cAMP levels and PDE10A enzyme is able to regulate these levels being highly expressed in striatum, its inhibitors emerged as useful drugs to mitigate this inflammatory process and hence the neuronal death associated with Parkinson’s disease (PD). Methodology & results: To study the utility of PDE10A as a pharmacological target for PD, in this work we propose the search and development of new PDE10A inhibitors that could be useful as pharmacological tools in models of the disease and presumably as potential drug candidates. By using different medicinal chemistry approaches we have discovered imidazole-like PDE10A inhibitors and showed their neuroprotective actions. Conclusion: Here, we demonstrate the neuroprotective effect of PDE10A inhibitors in cellular models of PD.

    Papers of special note have been highlighted as: • of interest

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