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Modulating P1 Adenosine Receptors in Disease Progression of SOD1G93A Mutant Mice

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Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal progressing neurodegenerative disease; to date, despite the intense research effort, only two therapeutic options, with very limited effects, are available. The purinergic system has been indicated as a possible new therapeutic target for ALS, but the results are often contradictory and generally confused. The present study was designed to determine whether P1 adenosine receptor ligands affected disease progression in a transgenic model of ALS. SOD1G93A mice were chronically treated, from presymptomatic stage, with a selective adenosine A2A receptor agonist (CGS21680), antagonist (KW6002) or the A1 receptor antagonist DPCPX. Body weight, motor performance and survival time were evaluated. The results showed that neither the stimulation nor the blockade of adenosine A2A receptors modified the progressive loss of motor skills or survival of mSOD1G93A mice. Conversely, blockade of adenosine A1 receptors from the presymptomatic stage significantly attenuated motor disease progression and induced a non-significant increase of median survival in ALS mice. Our data confirm that the modulation of adenosine receptors can elicit very different (and even opposite) effects during the progression of ALS course, thus strengthens the importance of further studies to elucidated their real therapeutic potential in this pathology.

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Authors and Affiliations

  1. National Center for Drug Research and Evaluation, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161, Rome, Italy

    Monica Armida, Alessandra Matteucci, Antonella Pèzzola, Patrizia Popoli & Rosa Luisa Potenza

  2. Department of Chemistry, Faculty of Science, Sultan Qaboos University, PO Box 36, 123, Muscat, Oman

    Younis Baqi

  3. PharmaCenter Bonn, Pharmazeutische Chemie I, Pharmazeutisches Institut, University of Bonn, Bonn, Germany

    Younis Baqi & Christa E. Müller

Authors
  1. Monica Armida
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  2. Alessandra Matteucci
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  3. Antonella Pèzzola
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  4. Younis Baqi
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  5. Christa E. Müller
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  6. Patrizia Popoli
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  7. Rosa Luisa Potenza
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All co-authors have seen and agree with the contents of the manuscript.

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Correspondence to Rosa Luisa Potenza.

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All procedures performed in studies involving animals were in accordance with the ethical standards of the institution and approved by the Italian Ministry of Health (Decree 118/2014B).

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Armida, M., Matteucci, A., Pèzzola, A. et al. Modulating P1 Adenosine Receptors in Disease Progression of SOD1G93A Mutant Mice. Neurochem Res 44, 1037–1042 (2019). https://doi.org/10.1007/s11064-019-02745-0

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  • DOI: https://doi.org/10.1007/s11064-019-02745-0

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