Taken together, evidence indicates that modulation of purinergic receptor expression and activity could be useful in PD treatment in several ways: (1) reducing microglia activation by damaged cells and α-synuclein aggregation through P2X7 and P2Y6 receptors antagonism; (2) preventing α-synuclein aggregation through P2X1 and A2A receptors antagonism; (3) modulating inflammatory scenario through A2A receptors antagonism; or (4) preventing dyskinesia induced by L-DOPA long-term use through combined treatment with A2A receptor antagonists. The gene discussed is P2RX7; the disease is Parkinson disease.