Nucleoside reverse transcriptase inhibitors and Kamuvudines inhibit amyloid-βinduced retinal pigmented epithelium degeneration

作     者：Siddharth Narendran Felipe Pereira Praveen Yerramothu Ivana Apicella Shao-bin Wang Kameshwari Ambati Shuichiro Hirahara Younghee Kim Meenakshi Ambati Vidya L.Ambati Peirong Huang Akhil Varshney Yosuke Nagasaka Shinichi Fukuda Kirstie L.Baker Kenneth M.Marion Jan M.Deussing Srinivas R.Sadda Bradley D.Gelfand Jayakrishna Ambati Siddharth Narendran;Felipe Pereira;Praveen Yerramothu;Ivana Apicella;Shao-bin Wang;Kameshwari Ambati;Shuichiro Hirahara;Younghee Kim;Meenakshi Ambati;Vidya L.Ambati;Peirong Huang;Akhil Varshney;Yosuke Nagasaka;Shinichi Fukuda;Kirstie L.Baker;Kenneth M.Marion;Jan M.Deussing;Srinivas R.Sadda;Bradley D.Gelfand;Jayakrishna Ambati

作者机构：Center for Advanced Vision ScienceUniversity of Virginia School of MedicineCharlottesvilleVAUSA Department of OphthalmologyUniversity of Virginia School of MedicineCharlottesvilleVAUSA Aravind Eye Care SystemMaduraiIndia Departamento de Oftalmologia e Ciências VisuaisEscola Paulista de MedicinaUniversidade Federal de São PauloSão PauloBrazil Center for Digital Image EvaluationCharlottesvilleVAUSA Doheny Eye InstituteLos AngelesLos AngelesCAUSA Molecular NeurogeneticsDepartment of Stress Neurobiology and NeurogeneticsMax Planck Institute of PsychiatryMunichGermany Department of OphthalmologyDavid Geffen School of MedicineUniversity of California–Los AngelesLos AngelesCAUSA Department of Biomedical EngineeringUniversity of Virginia School of MedicineCharlottesvilleVAUSA Department of PathologyUniversity of Virginia School of MedicineCharlottesvilleVAUSA Department of MicrobiologyImmunologyand Cancer BiologyUniversity of Virginia School of MedicineCharlottesvilleVAUSA 

出 版 物：《Signal Transduction and Targeted Therapy》 (信号转导与靶向治疗（英文）)

年 卷 期：2021年第6卷第5期

页      面：1526-1534页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100212[医学-眼科学] 10[医学] 

基　　金：J.A.has received support from NIH grants(R01EY028027,R01EY29799,R01EY031039) DuPont Guerry,III,Professorship,a gift from Mr.and Mrs.Eli W.Tullis,and the University of Virginia Strategic Investment Fund B.D.G.has received support from NIH grants(R01EY028027 and R01EY031039) BrightFocus Foundation,and the Owens Family Foundation 

主　　题：degeneration activation upstream 

摘      要：Nonfibrillar amyloid-βoligomers(AβOs)are a major component of drusen,the sub-retinal pigmented epithelium(RPE)extracellular deposits characteristic of age-related macular degeneration(AMD),a common cause of global *** report that AβOs induce RPE degeneration,a clinical hallmark of geographic atrophy(GA),a vision-threatening late stage of AMD that is currently *** demonstrate that AβOs induce activation of the NLRP3 inflammasome in the mouse RPE in vivo and that RPE expression of the purinergic ATP receptor P2RX7,an upstream mediator of NLRP3 inflammasome activation,is required for AβO-induced RPE *** classes of small molecule inflammasome inhibitors—nucleoside reverse transcriptase inhibitors(NRTIs)and their antiretrovirally inert modified analog Kamuvudines—both inhibit AβOs-induced RPE *** findings crystallize the importance of P2RX7 and NLRP3 in a disease-relevant model of AMD and identify inflammasome inhibitors as potential treatments for GA.