Indeed, activation of P2X7 by agonists in ALS primary microglia further aggravates pro-inflammatory responses, as NADPH oxidase 2 activity, reactive oxygen species production, tumor necrosis factor-α and cyclooxigenase-2 expression, microtubules associated protein kinases activation, miR-155, miR-125b, miR-146b up-regulation, and miR-22 down regulation, moreover causing direct toxicity towards ALS motor neuron cells (D’Ambrosi et al., 2009; Apolloni et al., 2013b; Parisi et al., 2013; Apolloni et al., 2014; Parisi et al., 2016). Here, TNF is linked to amyotrophic lateral sclerosis.