Krüppel-like factors:potential roles in blood-brain barrier dysfunction and epileptogenesis  

作　　者：Ana Beatriz Santos Andreia Carona Miren Ettcheto Antoni Camins Amílcar Falcão Ana Fortuna Joana Bicker 

机构地区：[1]University of Coimbra,Faculty of Pharmacy,Coimbra,Portugal [2]University of Coimbra,Coimbra Institute for Biomedical Imaging and Translational Research,Coimbra,Portugal [3]Biomedical Research Networking Center in Neurodegenerative Diseases(CIBERNED),Madrid,Spain [4]Department of Pharmacology,Toxicology and Therapeutic Chemistry,Faculty of Pharmacy and Food Science,Universitat de Barcelona,Barcelona,Spain [5]Institute of Neuroscience,Universitat de Barcelona,Barcelona,Spain [6]Institut d’InvestigacióSanitària Pere Virgili(IISPV),Reus,Spain

出　　处：《Acta Pharmacologica Sinica》2024年第9期1765-1776,共12页中国药理学报（英文版）

基　　金：The authors acknowledge Fundo Europeu de Desenvolvimento Regional(FEDER)through Portugal2020 in the scope of the Operational Programme for Competitiveness and Internationalization;Fundação para a Ciência e Tecnologia(FCT),Portuguese Agency for Scientific Research,within the scope of the research project 2022.03133.PTDC and Ph.D.research grant 2021.06125.BD;Spanish Ministerio de Ciencia e Innovación(PID2021-123462OB-I00);the Generalitat de Catalunya(2021 SGR 00288);CIBERNED(Grant CB06/05/2004);Institut de Neurociències UB,(CEX2021-001159-M).ME is Serra Hunter fellow.

摘　　要：Epilepsy is a chronic and debilitating neurological disorder,known for the occurrence of spontaneous and recurrent seizures.Despite the availability of antiseizure drugs,30%of people with epilepsy experience uncontrolled seizures and drug resistance,evidencing that new therapeutic options are required.The process of epileptogenesis involves the development and expansion of tissue capable of generating spontaneous recurrent seizures,during which numerous events take place,namely blood-brain barrier(BBB)dysfunction,and neuroinflammation.The consequent cerebrovascular dysfunction results in a lower seizure threshold,seizure recurrence,and chronic epilepsy.This suggests that improving cerebrovascular health may interrupt the pathological cycle responsible for disease development and progression.Krüppel-like factors(KLFs)are a family of zinc-finger transcription factors,encountered in brain endothelial cells,glial cells,and neurons.KLFs are known to regulate vascular function and changes in their expression are associated with neuroinflammation and human diseases,including epilepsy.Hence,KLFs have demonstrated various roles in cerebrovascular dysfunction and epileptogenesis.This review critically discusses the purpose of KLFs in epileptogenic mechanisms and BBB dysfunction,as well as the potential of their pharmacological modulation as therapeutic approach for epilepsy treatment.

关 键 词：blood-brain barrier cerebrovascular dysfunction EPIGENETICS epilepsy krüppel-like factors NEUROINFLAMMATION 

分 类 号：R742.1[医药卫生—神经病学与精神病学]