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

查看全文 作　　者：Talita [1]Glaser;Roberta [1]Andrejew;Agatha Oliveira-[1]Giacomelli;Deidiane Elisa [1]Ribeiro;Lucas Bonfim [1]Marques;Qing [1,2]Ye;Wen-Jing [2,5]Ren;Alexey [3,4]Semyanov;Peter [5,6]Illes;Yong [2,6]Tang;Henning [1]Ulrich

机构地区：[1]Department of Biochemistry,Institute of Chemistry,University of Sao Paulo,Av.Prof.Lineu Prestes 74&Sao 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 ftir Pharmakologie und Toxikologie,Universitat Leipzig,Leipzig 04107,Germany;[6]International Collaborative Centre on Big Science Plan for Purine Signaling,Chengdu University of Traditional Chinese Medicine,Chengdu 610075,China

出　　处：《Neuroscience Bulletin》索引2020年第36卷第11期,共16页

基　　金：the Sao Paulo Research Foundation(FAPESP,2018/07366-4);a Fellowship from the National Council for Scientific and Technological Development(CNPq,306392/2017-8);postdoctoral fellowships from FAPESP(2015/13345-1,2019/268520,and 2018/17504-5);a doctoral fellowship from FAPESP(2019/24553-5);a master fellowship from CNPq(133396/2019-3);the fellowship from National Key R&D Program of China(2019YFC1709101);The Project First-Class Disciplines Development(CZYHW1901)of Chengdu University of TCM and Sichuan Science and Technology Program(2019YFH0108,2018SZ0257);supported by Russian Science Foundation grant 20-14-00241。 摘　　要：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 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 Ca^2+signaling,might present interesting therapeutic potential for HD and PD. 关键词：Purinergic receptor Central nervous system Huntington’s disease Parkinson’s disease 6-HYDROXYDOPAMINE

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

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