Modulating P1 Adenosine Receptors in Disease Progression of SOD1 ^G93A Mutant Mice

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. SOD1 ^G93A mice were chronically treated, from presymptomatic stage, with a selective adenosine A _2A receptor agonist (CGS21680), antagonist (KW6002) or the A ₁ receptor antagonist DPCPX. Body weight, motor performance and survival time were evaluated. The results showed that neither the stimulation nor the blockade of adenosine A _2A receptors modified the progressive loss of motor skills or survival of mSOD1 ^G93A mice. Conversely, blockade of adenosine A ₁ 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.