Huntington’s (HD) and Parkinson’s diseases (PD) are neurodegenerative disorders caused by the death of GABAergic and dopaminergic neurons in the basal ganglia leading to hyperkinetic and hypokinetic symptoms, respectively. We review here the participation of purinergic receptors through intracellular Ca²⁺ signaling in these neurodegenerative diseases. The adenosine A_2A receptor stimulates striatopallidal GABAergic neurons, resulting in inhibitory actions on GABAergic neurons of the globus pallidus. A_2A and dopamine D2 receptors form functional heteromeric complexes inducing allosteric inhibition, and A_2A receptor activation results in motor inhibition. Furthermore, the A_2A receptor physically and functionally interacts with glutamate receptors, mainly with the mGlu5 receptor subtype. This interaction facilitates glutamate release, resulting in NMDA glutamate receptor activation and an increase of Ca²⁺ influx. P2X7 receptor activation also promotes glutamate release and neuronal damage. Thus, modulation of purinergic receptor activity, such as A_2A and P2X7 receptors, and subsequent aberrant Ca²⁺ signaling, might present interesting therapeutic potential for HD and PD.

亨廷顿病 (HD) 和帕金森病 (PD) 是由基底神经节中 GABA 能和多巴胺能神经元死亡引起的神经退行性疾病，分别导致运动过度和运动不足症状。我们在此回顾了嘌呤能受体通过细胞内 Ca ²⁺信号传导参与这些神经退行性疾病的过程。腺苷 A _2A受体刺激纹状体苍白球 GABA 能神经元，从而对苍白球 GABA 能神经元产生抑制作用。A _2A和多巴胺 D2 受体形成功能性异聚复合物，诱导变构抑制，A _2A受体激活导致运动抑制。此外，A _2A受体在物理上和功能上与谷氨酸受体相互作用，主要与mGlu5受体亚型相互作用。这种相互作用促进谷氨酸释放，导致 NMDA 谷氨酸受体激活并增加 Ca ²⁺流入。P2X7 受体激活还会促进谷氨酸释放和神经元损伤。因此，调节嘌呤能受体活性，例如 A _2A和 P2X7 受体，以及随后的异常 Ca ²⁺信号传导，可能为 HD 和 PD 带来有趣的治疗潜力。