典型文献
HACE1 negatively regulates neuroinflammation through ubiquitylating and degrading Rac1 in Parkinson's disease models
文献摘要：
Neuroinflammation plays an important role in neurodegenerative diseases,such as Parkinson's disease(PD)and Alzheimer's disease.HACE1(HECT domain and Ankyrin repeat Containing E3 ubiquitin-protein ligase 1)is a tumor suppressor.Recent evidence suggests that HACE1 may be involved in oxidative stress responses.Due to the critical role of ROS in neuroinflammation,we speculated that HACE1 might participate in neuroinflammation and related neurodegenerative diseases,such as PD.In this study,we investigated the role of HACE1 in neuroinflammation of PD models.We showed that HACE1 knockdown exacerbated LPS-induced neuroinflammation in BV2 microglial cells in vitro through suppressing ubiquitination and degradation of activated Rac1,an NADPH oxidase subunit.Furthermore,we showed that HACE1 exerted vital neuronal protection through increasing Rac1 activity and stability in LPS-treated SH-SY5Y cells,as HACE1 knockdown leading to lower tolerance to LPS challenge.In MPTP-induced acute PD mouse model,HACE1 knockdown exacerbated motor deficits by activating Rac1.Finally,mutant α-synuclein(A53T)-overexpressing mice,a chronic PD mouse model,exhibited age-dependent reduction of HACE1 levels in the midbrain and striatum,implicating that HACE1 participated in PD pathological progression.This study for the first time demonstrates that HACE1 is a negative regulator of neuroinflammation and involved in the PD pathogenesis by regulating Rac1 activity.The data support HACE1 as a potential target for PD and other neurodegenerative diseases.
文献关键词：
中图分类号：
作者姓名：
Cai-xia Zang;Lu Wang;Han-yu Yang;Jun-mei Shang;Hui Liu;Zi-hong Zhang;Cheng Ju;Fang-yu Yuan;Fang-yuan Li;Xiu-qi Bao;Dan Zhang
作者机构：
State Key Laboratory of Bioactive Substance and Function of Natural Medicines,Department of Pharmacology,Institute of Materia Medica,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100050,China
文献出处：
引用格式：
[1]Cai-xia Zang;Lu Wang;Han-yu Yang;Jun-mei Shang;Hui Liu;Zi-hong Zhang;Cheng Ju;Fang-yu Yuan;Fang-yuan Li;Xiu-qi Bao;Dan Zhang-.HACE1 negatively regulates neuroinflammation through ubiquitylating and degrading Rac1 in Parkinson's disease models)[J].中国药理学报（英文版）,2022(02):285-294
A类：
HACE1,ubiquitylating,Ankyrin
B类：
negatively,regulates,neuroinflammation,through,degrading,Rac1,Parkinson,models,Neuroinflammation,plays,important,role,neurodegenerative,diseases,such,Alzheimer,HECT,domain,repeat,Containing,E3,protein,ligase,tumor,suppressor,Recent,evidence,suggests,that,may,be,involved,oxidative,stress,responses,Due,critical,ROS,speculated,might,related,In,this,study,investigated,We,showed,knockdown,exacerbated,LPS,induced,BV2,microglial,cells,vitro,suppressing,ubiquitination,degradation,activated,NADPH,oxidase,subunit,Furthermore,exerted,vital,neuronal,protection,increasing,activity,stability,treated,SH,SY5Y,leading,lower,tolerance,challenge,MPTP,acute,mouse,motor,deficits,by,activating,Finally,mutant,synuclein,A53T,overexpressing,mice,chronic,exhibited,age,dependent,reduction,levels,midbrain,striatum,implicating,participated,pathological,progression,This,first,demonstrates,regulator,pathogenesis,regulating,data,support,potential,target,other
AB值：
0.521074
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