P2RX4 and amyotrophic lateral sclerosis: Furthermore, it was observed that the upregulation of P2X4, P2X7, and P2Y6 receptors in mSOD1 microglia, in particular P2X7, was associated with reduced ATP hydrolysis in the same ALS microglia, which led to increased production of tumor necrosis factor (TNF)-α and cyclooxygenase-2 (COX-2) with consequent toxicity to neuronal cells (60).