The role of the brain renin-angiotensin system in Parkinson's disease  

作　　者：Jose Luis Labandeira-Garcia Carmen M.Labandeira Maria J.Guerra Ana I.Rodriguez-Perez 

机构地区：[1]Cellular and Molecular Neurobiology of Parkinson'S Disease,Research Center for Molecular Medicine and Chronic Diseases(CIMUS),IDIS,University of Santiago de Compostela,Santiago de Compostela 15782,Spain [2]Networking Research Center On Neurodegenerative Diseases(CIBERNED),Madrid,Spain [3]Neurology Service,University Hospital of Ourense,Ourense,Spain

出　　处：《Translational Neurodegeneration》2024年第1期809-827,共19页转化神经变性病(英文)

基　　金：supported by Spanish Ministry of Science and Innovation(PID2021-126848NB-I00,PLEC2022-009401);Instituto de Salud CarlosⅢ(RD21/0017/0031;PI20/00345,and CIBERNED);Galician Government(XUGA,ED431C 2022/41),and FEDER(Regional European Development Fund).

摘　　要：The renin-angiotensin system(RAS)was classically considered a circulating hormonal system that regulates blood pressure.However,different tissues and organs,including the brain,have a local paracrine RAS.Mutual regulation between the dopaminergic system and RAS has been observed in several tissues.Dysregulation of these interactions leads to renal and cardiovascular diseases,as well as progression of dopaminergic neuron degeneration in a major brain center of dopamine/angiotensin interaction such as the nigrostriatal system.A decrease in the dopaminergic function induces upregulation of the angiotensin type-1(AT1)receptor activity,leading to recovery of dopamine levels.However,AT1 receptor overactivity in dopaminergic neurons and microglial cells upregulates the cellular NADPH-oxidase-superoxide axis and Ca^(2+)release,which mediate several key events in oxidative stress,neuroinflammation,andα-synuclein aggregation,involved in Parkinson’s disease(PD)pathogenesis.An intraneuronal antioxidative/anti-inflammatory RAS counteracts the effects of the pro-oxidative AT1 receptor overactivity.Consistent with this,an imbalance in RAS activity towards the pro-oxidative/pro-inflammatory AT1 receptor axis has been observed in the substantia nigra and striatum of several animal models of high vulnerability to dopaminergic degeneration.Interestingly,autoantibodies against angiotensin-converting enzyme 2 and AT1 receptors are increased in PD models and PD patients and contribute to blood-brain barrier(BBB)dysregulation and nigrostriatal pro-inflammatory RAS upregulation.Therapeutic strategies addressed to the modulation of brain RAS,by AT1 receptor blockers(ARBs)and/or activation of the antioxidative axis(AT2,Mas receptors),may be neuroprotective for individuals with a high risk of developing PD or in prodromal stages of PD to reduce progression of the disease.

关 键 词：ANGIOTENSIN DOPAMINE NADPH-OXIDASE NEURODEGENERATION Neuroprotection NEUROINFLAMMATION Oxidative stress PARKINSON 

分 类 号：R73[医药卫生—肿瘤]