In addition, it was found that up-regulation of P2Y6, P2X7, and P2X4 receptors in mSOD1 microglia, is associated with decreased hydrolysis of ATP in the same microglial ALS, which induces elevated synthesis of cyclooxygenase-2 (COX-2) and tumor necrosis factor-alpha (TNF-α) with consequent toxic effect to neurons [105]. This evidence concerns the gene PTGS2 and amyotrophic lateral sclerosis.