NADPH氧化酶在帕金森病中的作用_郑远鹏

《NADPH氧化酶在帕金森病中的作用_郑远鹏》由会员上传分享，免费在线阅读，更多相关内容在行业资料-天天文库。

1、ChineseJournalofNewDrugs2016,25(8)·综述·NADPH氧化酶在帕金森病中的作用郑远鹏，鲍秀琦，孙华，张丹(中国医学科学院北京协和医学院药物研究所，天然药物活性物质与功能国家重点实验室，北京100050)［摘要］帕金森病(Parkinson’sdisease，PD)是与衰老相关的神经退行性疾病。氧化应激和神经炎症在PD的发病中起着重要作用，小胶质细胞中还原型烟酰胺腺嘌呤二核苷酸磷酸(nicotinamideadeninedinu-cleotidephosphate，NADPH)氧化酶是触发氧化应激和神经炎症的关键酶，

2、是生成活性氧簇(reactiveoxygenspecies，ＲOS)的主要来源。ＲOS可激活炎症信号通路而引起炎症反应，释放的炎症因子和过量的ＲOS可损伤多巴胺能神经元，导致神经退行性病变和PD的发生。抑制NADPH氧化酶可减轻多巴胺能神经元丢失，改善PD症状。因此NADPH氧化酶是PD发病的重要分子机制，对其在PD发病中的作用研究有助于推动以NADPH氧化酶为靶点治疗PD新药的研发，同时为开发以抗氧化及抗炎为作用机制治疗PD的药物提供理论依据。［关键词］帕金森病;NADPH氧化酶;活性氧簇;氧化应激;神经炎症［中图分类号］Ｒ96［文献标志码］A

3、［文章编号］1003－3734(2016)08－0872－07ＲolesofNADPHoxidaseinthepathogenesisofParkinson’sdiseaseZHENGYuan-peng，BAOXiu-qi，SUNHua，ZHANGDan(StateKeyLaboratoryofNaturalProductsandFunctions，InstituteofMateriaMedica，ChineseAcademyofMedicalSciences＆PekingUnionMedicalCollege，Beijing100050，Chi

4、na)［Abstract］Parkinson’sdiseaseisaneurodegenerativedisorderrelatedtoaging，characterizedbyprogres-sivelossofdopaminergicneuronsinsubstantianigra．Althoughthepathologicalmechanismisnotfullyestablished，theoxidativestressresponseandneuroinflammationtriggeredbynicotinamideadeninedi

5、nucleotidephosphate(NADPH)oxidase，amembrane-boundenzymecomplex，appeartoplayacentralroleinthepathogenesisofPD．Thestimulationofmicroglialeadstothephosphorylationandtranslocationofthep47phoxandp67phoxcytosolicsubunits，activationofmembrane-boundPHOX，andtheproductionofＲOS．TheNADPH

6、oxidase-derivedＲOSiskeysignalingmoleculesthattriggertheprogressionofinflammatoryresponse．Thereleasedcytokinesduringinflam-mationaretoxictodopaminergicneurons，whichresultsinneurodegenerationandthedevelopmentofPD．Inaddi-tion，inhibitionofNADPHoxidasereducesthelossofdopaminergicn

7、euronsandimprovesthemotorfunctionofPD．Therefore，NADPHoxidase-mediatedoxidativestressandneuroinflammationisamainmechanisminthepath-ogenesisofPD，andinhibitionofthisenzymemayprovidenoveltherapiesforPD．ThusitisofgreatsignificancetofindnewcompoundstargetingatNADPHoxidaseasneuropro

8、tectiveagentstodelaytheprogressofPD．［Keywords］Parkinson’sdisease;NAD