Purinergic Receptors in Basal Ganglia Diseases: Shared Molecular Mechanisms between Huntington's and Parkinson's Disease

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 Ca(2+)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 Ca(2+)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 Ca(2+)signaling, might present interesting therapeutic potential for HD and PD. (AU)