Normally, signaling of the A2A-R sequentially couples with GSα and involves activation of adenylyl cyclase, formation of cAMP, stimulation of PKA, and phosphorylation activation of the CREB at Ser133 [30], [35], [36], which plays a pivotal role in neuronal survival [37] and genetic models of HD [38]. The gene discussed is CREB1; the disease is Huntington disease.