P2RX4 and amyotrophic lateral sclerosis: With regards purinergic signaling and ALS, an up-regulation of P2X4, P2X7, and P2Y6 receptors has been observed in transgenic mice over-expressing human superoxide dismutase 1 (SOD1), an animal model of ALS (D’Ambrosi et al., 2009), as well as the down-regulation of ATP-hydrolyzing activities in microglia, suggesting that the pro-inflammatory actions of microglial P2 receptors are enhanced in this ALS model.