Adenosine and Adenosine A_2AReceptors as Targets for the Treatment of Niemann Pick Type C Disease

Abstract

Niemann Pick type C (NPC) is a rare neurovisceral disorder characterized by progressive hepatosplenomegaly, neurodegeneration, and premature death; it is caused by mutations in genes coding for two lysosomal proteins: the transmembrane NPC1 and the soluble NPC2. Mutations in both of them cause intracellular accumulation of cholesterol and other lipids in the endo/lysosomal compartment. Currently, an inhibitor of glycosphingolipid synthesis is the only drug approved by the European Medicines Agency, but it only reduces rate of disease progression; for this reason, the search for new druggable targets is urgent. In the present review, the adenosinergic system with a particular focus onto the adenosine A 2A receptor will be presented as a potential therapeutic target for NPC and results obtained in cellular and animal models of the disease will be discussed.