Modulating P1 Adenosine Receptors in Disease Progression of SOD1G93A Mutant Mice

Monica Armida, Alessandra Matteucci, Antonella Pèzzola, Younis Baqi, Christa E Müller, Patrizia Popoli, Rosa Luisa Potenza

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1037-1042
Number of pages6
JournalNeurochemical Research
Volume44
Issue number5
DOIs
Publication statusPublished - May 2019

Keywords

  • Adenosine/analogs & derivatives
  • Amyotrophic Lateral Sclerosis/drug therapy
  • Animals
  • Disease Models, Animal
  • Mice, Transgenic
  • Microglia/drug effects
  • Motor Neurons/drug effects
  • Phenethylamines/pharmacology
  • Receptors, Purinergic P1/drug effects
  • Spinal Cord/drug effects
  • Superoxide Dismutase-1/drug effects

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