Keap1/Nrf2/ARE signaling unfolds therapeutic targets for redox imbalanced-mediated diseases and diabetic nephropathy

被引：99

作者：

Adelusi, Temitope Isaac ^{[1
]}

Du, Lei ^{[1
]}

Hao, Meng ^{[1
]}

Zhou, Xueyan ^{[1
]}

Xuan, Qian ^{[1
]}

Apu, Chowdhury ^{[1
]}

Sun, Ying ^{[1
]}

Lu, Qian ^{[1
]}

Yin, Xiaoxing ^{[1
]}

机构：

[1] Xuzhou Med Univ, Jiangsu Key Lab New Drug Res & Clin Pharm, Xuzhou 221004, Jiangsu, Peoples R China

来源：

BIOMEDICINE & PHARMACOTHERAPY | 2020年 / 123卷

基金：

中国国家自然科学基金;

关键词：

Diabetic nephropathy; Keap1/Nrf2/ARE signaling; Oxidative stress; Antioxidant agents; Diabetic nephropathy biomarkers; GLYCATION END-PRODUCTS; RENIN-ANGIOTENSIN SYSTEM; NF-KAPPA-B; TRANSCRIPTION FACTOR NRF2; CONVERTING ENZYME-INHIBITORS; NEUTRALIZING RAGE-ANTIBODY; GLOMERULAR-FILTRATION-RATE; SUBSTRATE ADAPTER PROTEIN; CUL3-BASED E3 LIGASE; TISSUE GROWTH-FACTOR;

D O I：

10.1016/j.biopha.2019.109732

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Hyperglycemia/oxidative stress has been implicated in the initiation and progression of diabetic complications while the components of Keap1/Nrf2/ARE signaling are being exploited as therapeutic targets for the treatment/management of these pathologies. Antioxidant agents like drugs, nutraceuticals and pure compounds that target the proteins of this pathway and their downstream genes hold the therapeutic strength to put the progression of this disease at bay. Here, we elucidate how the modulation of Keap1/Nrf2/ARE had been exploited for the treatment/management of end-stage diabetic kidney complication (diabetic nephropathy) by looking into (1) Nrf2 nuclear translocation and phosphorylation by some protein kinases at specific amino acid sequences and (2) Keap1 downregulation/Keap1-Nrf2 protein-protein inhibition (PPI) as potential therapeutic mechanisms exploited by Nrf2 activators for the modulation of diabetic nephropathy biomarkers (Collagen IV, Laminin, TGF-beta-1 and Fibronectin) that ultimately lead to the amelioration of this disease progression. Furthermore, we brought to limelight the relationship between diabetic nephropathy and Keap1/Nrf2/ARE and finally elucidate how the modulation of this signaling pathway could be further explored to create novel therapeutic milestones.

引用

页数：20

共 233 条

[1] Discovery of direct inhibitors of Keap1-Nrf2 protein-protein interaction as potential therapeutic and preventive agents [J].