Targeting the adenosine A2A receptor for neuroprotection and cognitive improvement in traumatic brain injury and Parkinson's disease  

作　　者：Yan Zhao Yuan-Guo Zhou Jiang-Fan Chen 

机构地区：[1]Department of Army Occupational Disease,State Key Laboratory of Trauma,Burns and Combined Injury,Research Institute of Surgery,Daping Hospital,Army Medical University.Chongqing,400042,China [2]The Molecular Neuropharmacology Laboratory and the Eye-Brain Research Center,The State Key Laboratory of Ophthalmology,Optometry and Vision Science,Wenzhou Medical University,Wenzhou,325035,Zhejiang Province,China [3]Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine,Vision and Brain Health),Wenzhou,325035,Zhejiang Province,China

出　　处：《Chinese Journal of Traumatology》2024年第3期125-133,共9页中华创伤杂志（英文版）

基　　金：supported in part by the grants from the National Natural Science Foundation of China[grant numbers 81771176 for Zhao Y,82150710558 and 82151308 for Chen JF];by the Startup Funds from the Oujiang Laboratory (the Zhejiang Provincial Key Laboratory for Regenerative Medicine and Eye-Brain Disorders)[grant number OJQDSP2022007 for Chen JF]Wenzhou,China。

摘　　要：Adenosine exerts its dual functions of homeostasis and neuromodulation in the brain by acting at mainly 2 G-protein coupled receptors,called A1 and A2A receptors.The adenosine A2A receptor(A2AR)antagonists have been clinically pursued for the last 2 decades,leading to final approval of the istradefylline,an A2AR antagonist,for the treatment of OFF-Parkinson's disease(PD)patients.The approval paves the way to develop novel therapeutic methods for A2AR antagonists to address 2 major unmet medical needs in PD and traumatic brain injury(TBI),namely neuroprotection or improving cognition.In this review,we first consider the evidence for aberrantly increased adenosine signaling in PD and TBI and the sufficiency of the increased A2AR signaling to trigger neurotoxicity and cognitive impairment.We further discuss the increasing preclinical data on the reversal of cognitive deficits in PD and TBI by A2AR antagonists through control of degenerative proteins and synaptotoxicity,and on protection against TBI and PD pathologies by A2AR antagonists through control of neuroinflammation.Moreover,we provide the supporting evidence from multiple human prospective epidemiological studies which revealed an inverse relation between the consumption of caffeine and the risk of developing PD and cognitive decline in aging population and Alzheimer's disease patients.Collectively,the convergence of clinical,epidemiological and experimental evidence supports the validity of A2AR as a new therapeutic target and facilitates the design of A2AR antagonists in clinical trials for disease-modifying and cognitive benefit in PD and TBI patients.

关 键 词：Receptor Adenosine A2A Adenosine A2 receptor antagonists Parkinson's disease Brain injuries traumatic 

分 类 号：R651.15[医药卫生—外科学] R742.5[医药卫生—临床医学]