多功能 APE1 DNA 修复-氧化还原信号蛋白作为人类疾病的药物靶点。
The multifunctional APE1 DNA repair-redox signaling protein as a drug target in human disease.
机构信息
Herman B. Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, 1044 W. Walnut, Indianapolis, IN 46202, USA.
Apexian Pharmaceuticals, 20 N Meridian St, Indianapolis, IN 46204, USA.
出版信息
Drug Discov Today. 2021 Jan;26(1):218-228. doi: 10.1016/j.drudis.2020.10.015. Epub 2020 Oct 24.
Abstract
Apurinic/apyrimidinic (AP) endonuclease-reduction/oxidation factor 1 (APE1/Ref-1, also called APE1) is a multifunctional enzyme with crucial roles in DNA repair and reduction/oxidation (redox) signaling. APE1 was originally described as an endonuclease in the Base Excision Repair (BER) pathway. Further study revealed it to be a redox signaling hub regulating critical transcription factors (TFs). Although a significant amount of focus has been on the role of APE1 in cancer, recent findings support APE1 as a target in other indications, including ocular diseases [diabetic retinopathy (DR), diabetic macular edema (DME), and age-related macular degeneration (AMD)], inflammatory bowel disease (IBD) and others, where APE1 regulation of crucial TFs impacts important pathways in these diseases. The central responsibilities of APE1 in DNA repair and redox signaling make it an attractive therapeutic target for cancer and other diseases.
摘要
脱嘌呤/脱嘧啶（AP）内切核酸酶修复/氧化因子 1（APE1/Ref-1，也称为 APE1）是一种多功能酶，在 DNA 修复和氧化还原（redox）信号中起着关键作用。APE1 最初被描述为碱基切除修复（BER）途径中的内切核酸酶。进一步的研究表明，它是一个氧化还原信号枢纽，调节关键转录因子（TFs）。尽管人们对 APE1 在癌症中的作用给予了极大的关注，但最近的研究结果支持 APE1 作为其他适应症的靶点，包括眼部疾病[糖尿病视网膜病变（DR）、糖尿病黄斑水肿（DME）和年龄相关性黄斑变性（AMD）]、炎症性肠病（IBD）和其他疾病，在这些疾病中，APE1 对关键 TFs 的调节会影响这些疾病中的重要途径。APE1 在 DNA 修复和氧化还原信号中的核心作用使其成为癌症和其他疾病有吸引力的治疗靶点。
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