P2Y12 receptor is activated by endogenous agonist ADP (EC50 = 60 nM).221 It acts as a regulator of blood clotting; therefore, it is targeted for the treatment of thromboembolisms.290 In normal brain, P2Y12R expression level is high on M2 type microglia291 but downregulates under pathological conditions or after LPS treatment.291,292 Indeed, expression of P2Y12 in microglia was undetectable 24 hours after injury.16 During microglial transition from highly ramified to an amoeboid state, low level of P2Y12 receptors is an indication of the receptor role in early responses of microglia to the brain injury.16 Immunohistochemical studies of postmortem brains from patients with AD and MS have shown reduction of P2Y12 receptor expression on microglia near the injury sites.291 Therefore, P2Y12 receptor could potentially act as a valuable biomarker for detecting the activity of human microglia during CNS pathologies in neurodegenerative diseases.291 P2Y12 is also expressed on astrocytes of the rat cortex and hippocampal pyramidal neurons and on oligodendrocytes where is involved in myelination.271,293
