P2Y12, also referred to as P2RY12 or P2Y12R, is a Gi – coupled purinoceptor and is of particular relevance for microglia in the central nervous system (CNS) (1). The preferred agonist is ADP, the degradation product of ATP, which is released from neurons and other glial cells during physiological activity or after tissue damage. P2Y12 receptor is highly expressed in processes and somata of surveilling microglia and plays a major role in microglial chemotaxis in response to local CNS injury (2). More recently, P2Y12 receptors have been shown to be concentrated at microglia process-neuronal somata contacts (3) and to be critical for neuroprotection. To date, P2Y12 receptor is one of the most accepted microglia-specific markers used to distinguish CNS-resident microglia from CNS-associated macrophages (CAMs) and infiltrating monocytes/macrophages (4). The expression level of P2Y12 receptor is downregulated in an activated state of microglia referred to as disease-associated microglia (DAM). In the periphery, P2Y12 receptor is expressed in platelets and is a well-known biological target for anti-thrombotic drugs due to its central role in platelet activation, aggregation and blood clotting (5).
