P2X7R is regarded as an important silent receptor as its expression is only upregulated when ATP concentration increases to a high level,177 suggesting the high relevance of P2X7Rs in pathological conditions.178 P2X7Rs are expressed on presynaptic neurons, astrocytes, and oligodendrocytes, but its highest concentrations is expressed on microglia where it releases pro-inflammatory cytokine IL-1β, a key mediator of chronic inflammation and chronic pain.6,178 Several studies of the P2X7 receptors have shown involvement of this receptor in animal models of neuroinflammatory diseases including AD,137,179,180 PD,181 HD,182 FD,1 ALS,183 MS,184 TBI,15 cerebral ischemia,6 epilepsy,185 depression,186,187 anxiety, and bipolar disorders.178 Astrocytic P2X7Rs expression has also shown to be involved in the neurotoxic phenotype model of ALS.188
