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γ-分泌酶抑制剂在肾脏病发病机制中的研究进展
作者:王艳娇  李均 
单位:遵义医学院珠海校区 中药应用与基础研究重点实验室, 广东 珠海 519100
关键词:γ-分泌酶 γ-分泌酶抑制剂 肾脏病 作用机制 文献综述 
分类号:R692.6
出版年·卷·期(页码):2019·47·第一期(105-108)
摘要:

肾脏在受到病理因素刺激时Notch信号通路被重新激活。γ-分泌酶可特异性切割水解Notch受体配体的结合体,诱导促肾损害的信号网激活,加速肾脏病的进展。新近研究发现,酶复合物抑制剂可延缓肾脏病进程,有望成为肾脏病的靶点治疗药物。作者对γ-分泌酶抑制剂在肾脏病发病机制中的研究进展作一综述。

参考文献:

[1] 卓琳,蔡卿卿,刘丁阳,等.慢性肾脏病的患病率及危险因素荟萃分析[J].中国老年学杂志,2018,38(9):2135-2138.
[2] 康阳阳.中国成人慢性肾脏病患病率Meta分析[D].郑州:郑州大学,2017:1-77.
[3] ASANUMA K,OLIVA TREJO A,TANAKA E.The role of Notch signaling in kidney podocytes[J].Clin Exp Nephrol,2017,21(1):1-6.
[4] HU B,PHAN S H.Notch in fibrosis and as a target of anti-fibrotic therapy[J].Pharmacol Res,2016,108:57-64.
[5] 齐佩瑾.与阿尔茨海默症相关的γ-分泌酶复合物的表达与纯化研究[D].上海:上海交通大学,2015.
[6] BAI X C,YAN C,YANG G,et al.An atomic structure of human γ-secretase[J].Nature,2015,525(7568):212-217.
[7] BAI X C,RAIENDRA E,YANG G,et al.Sampling the conformational space of the catalytic subunit of human γ-secretase[J].Elife,2015,4(3):235-241.
[8] 张锦巍,井丽娟,孙亚平,等.引起阿尔茨海默病的γ-分泌酶作用机制[J].生物技术世界,2012,10(12):8-10.
[9] JUNG M E,METZGR D B,DAS H K.The role of presenilin-1 in the excitotoxicity of ethanol withdrawal[J].J Pharmacol Exp Ther,2016,358(3):516-526.
[10] CARROLL C,LI Y M.Physiological and pathological roles of the γ-secretase complex[J].Brain Res Bull,2016,126(Pt 2):199-206.
[11] AUNG K L,EI-KHOUEIRY A B,GELMON K,et al.A multi-arm phase Ⅰ dose escalating study of an oral NOTCH inhibitor BMS-986115 in patients with advanced solid tumours[J].Invest New Drugs,2018,36(6):1026-1036.
[12] MOHAMED A A,TAN S H,XAVIER C P,et al.Synergistic activity with NOTCH inhibition and androgen ablation in ERG-positive prostate cancer cells[J].Mol Cancer Res,2017,15(10):1308-1317.
[13] 叶旋.番荔枝酰胺衍生物(FLZ)选择性抑制γ-分泌酶改善线粒体功能及相关机制研究[D].北京:北京协和医学院,2012.
[14] 鄢浩.兼有神经保护作用的γ-分泌酶抑制剂的计算机辅助设计、合成及初步活性实验研究[D].武汉:华中科技大学,2006.
[15] CRUMP C J,MURREY H E,BALLARD T E,et al.Development of sulfonamide photoaffinity inhibitors for probing cellular γ-secretase[J].ACS Chem Neurosci,2016,7(8):1166-1173.
[16] GERTSIK N,AM ENDE C W,GEOGHEGAN K F.Mapping the binding site of BMS-708163 on γ-secretase with cleavable photoprobes[J].Cell Chem Biol,2017,24(1):3-8.
[17] SEKIOKA R,HONJO E,HONDA S,et al.Discovery of novel scaffolds for γ-secretase modulators without an arylimidazole moiety[J].Bioorg Med Chem,2018,26(2):435-442.
[18] 韦云,刘美霞,梁晓东,等.还脑益聪方提取物含药血清对APP/PS1双基因转染细胞γ分泌酶活性及相关蛋白表达的影响[J].中国药理学通报,2017,33(3):417-426.
[19] CHAU D M,SHUM D,RADU C,et al.A novel high throughput 1536-well Notch1 γ-secretasealpha LISA assay[J].Comb Chem High Throughput Screen,2013,16(6):415-424.
[20] 杨永凯.DAPT阻断Notch信号通路对人脑胶质瘤细胞系U251增殖和凋亡的影响[D].福州:福建医科大学,2009.
[21] LV W,BOOZ G W,FAN F,et al.Oxidative stress and renal fibrosis:recent insights for the development of novel therapeutic strategies[J].Front Physiol,2018,9(1):105.
[22] WU K,HU L,HOU J.Selective suppression of Notch1 inhibits proliferation of renal cell carcinoma cells through JNK/p38 pathway[J].Oncol Rep,2016,35(5):2795-2800.
[23] KIDA Y,ZULLO J A,GOLIGORSKY M S.Endothelial sirtuin 1 inactivation enhances capillary rarefaction and fibrosis following kidney injury through Notch activation[J].Biochem Biophys Res Commun,2016,478(3):1074-1079.
[24] EDELING M,RAGI G,HUANG S,et al.Developmental signalling pathways in renal fibrosis:the roles of Notch,Wnt and Hedgehog[J].Nat Rev Nephrol,2016,12(7):426-439.
[25] LIU B C,TANG T T,LV L L,et al.Renal tubule injury:a driving force toward chronic kidney disease[J].Kidney Int,2018,93(3):568-579.
[26] LAVOZ C,POVEDA J,MARQUEZ-EXPOSITO L,et al.Gremlin activates the Notch pathway linked to renal inflammation[J].Clin Sci (Lond),2018,132(11):1097-1115.
[27] ZHAO Y,QIAO X,WANG L.Matrix metalloproteinase 9 induces endothelial-mesenchymal transition via Notch activation in human kidney glomerular endothelial cells[J].BMC Cell Biol,2016,17(1):21.
[28] 洪炜龙,陆红,吴存造,等.γ-分泌酶抑制剂DAPT抑制Notch信号逆转马兜铃酸诱导的肾小管细胞表型转化[J].中国药理学与毒理学杂志,2016,30(3):209-214.
[29] TUNG C W,HSU Y C,CAI C J,et al.Trichostatin A ameliorates renal tubulointerstitial fibrosis through modulation of the JNK-dependent Notch-2 signaling pathway[J].Sci Rep,2017,7(1):14495.
[30] YAO M,GAO F,WANG X,et al.Nox4 is involved in high glucose-induced apoptosis in renal tubular epithelial cells via Notch pathway[J].Mol Med Rep,2017,15(6):4319-4325.
[31] KRAMER J,SCHWANBECK R,PAGEL H,et al.Inhibition of Notch signaling ameliorates acute kidney failure and downregulates platelet-derived growth factor receptor β in the mouse model[J].Cells Tissues Organs,2016,201(2):109-117.
[32] JUILLERAT-JEANNERET L,FLOHR A,SCHNEIDER M,et al.Targeted γ-secretase inhibition to control the notch pathway in renal diseases[J].J Med Chem,2015,58(20):8097-8109.
[33] 庞亮,刘光明,宋文利,等.Notch4在肾细胞癌中的表达及其与微血管密度的关系[J].实用医学杂志,2017,33(15):2525-2529.
[34] BHAGAT T D,ZOU Y,HUANG S,et al.Notch pathway is activated via genetic and epigenetic alterations and is a therapeutic target in clear cell renal cancer[J].J Biol Chem,2017,292(3):837-846.
[35] ROJAS J D,LIN F,CHIANG Y C,et al.Ultrasound molecular imaging of vegfr-2 in clear-cell renal cell carcinoma tracks disease response to antiangiogenic and notch-inhibition therapy[J].Theranostics,2018,8(1):141-155.
[36] HOLTTA M,DEAN R A,SIEMERS E,et al.A single dose of the γ-secretase inhibitor semagacestat alters the cerebrospinal fluid peptidome in humans[J].Alzheimers Res Ther,2016,8(1):11.
[37] STAGNI F,RASPANTI A,GIACOMINI A,et al.Long-term effect of neonatal inhibition of APP gamma-secretase on hippocampal development in the Ts65Dn mouse model of Down syndrome[J].Neurobiol Dis,2017,103:11-23.
[38] LOCONTE N K,RAZAK A R,IVY P,et al.A multicenter phase 1 study of γ-secretase inhibitor RO4929097 in combination with capecitabine in refractory solid tumors[J].Invest New Drugs,2015,33(1):169-176.
[39] LOCATELLI M A,AFTIMOS P,DEES E C,et al.Phase I study of the gamma secretase inhibitor PF-03084014 in combination with docetaxel in patients with advanced triple-negative breast cancer[J].Oncotarget,2017,8(2):2320-2328.
[40] 钟丽娟,王婷,何紫阳,等.单味活血化瘀中药抗肾纤维化的实验研究概况[J].中国民族民间医药,2016,25(6):40-43.

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