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

Talita Glaser 1• Roberta Andrejew 1• A ´ gatha Oliveira-Giacomelli 1•Deidiane Elisa Ribeiro 1• Lucas Bonfim Marques 1• Qing Ye 1,2• Wen-Jing Ren 2,5•Alexey Semyanov 3,4• Peter Illes 5,6
• Yong Tang 2,6• Henning Ulrich 1


1 Department of Biochemistry, Institute of Chemistry, University of Sa˜o Paulo, Av. Prof. Lineu Prestes 748, Sa˜o Paulo, SP 05508-000, Brazil
2 Key Laboratory of Sichuan Province for Acupuncture and Chronobiology, Chengdu 610075, China
3 Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997, Russia
4 Sechenov First Moscow State Medical University, Moscow 119992, Russia
5 Rudolf-Boehm-Institut fu¨r Pharmakologie und Toxikologie, Universita¨t Leipzig, Leipzig 04107, Germany
6 International Collaborative Centre on Big Science Plan for Purine Signaling, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China

Abstract

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 A2A receptor stimulates striatopallidal GABAergic neurons, resulting in inhibitory actions on GABAergic neurons of the globus pallidus. A2A and dopamine D2 receptors form functional heteromeric complexes inducing allosteric inhibition, and A2A receptor activation results in motor inhibition. Furthermore, the A2A 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 A2A and P2X7 receptors, and subsequent aberrant Ca2+ signaling, might present interesting therapeutic potential for HD and PD.


 

Keywords

Purinergic receptor;  Central nervous system; Huntington’s disease;  Parkinson’s disease ; 6-hydroxydopamine

[SpringerLink]

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