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Journal of Cellular Signaling

ISSN: 2692-0638

Commentary Open Access
Volume 2 | Issue 2 | DOI: https://doi.org/10.33696/Signaling.2.044

APE1/Ref-1 as a Novel Target for Retinal Diseases

Curtis Heisel2, Jonah Yousif2, Mahmut Mijiti1, Kostas Charizanis3, Mitchel Brigell4, Timothy W. Corson5,6,7,8, Mark R. Kelley1,5,6,7,8,*
  • 1Herman B Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, 1044 W. Walnut St., Indianapolis, IN 46202, USA
  • 2University of Michigan Medical School, 1301 Catherine St, Ann Arbor, MI 48105, USA
  • 3Independent Consultant, Livonia, MI 48150, USA
  • 4Ocuphire Pharma Inc., Farmington Hills, MI, USA
  • 5Department of Pharmacology and Toxicology, Indiana University School of Medicine, 1044 W. Walnut St., Indianapolis, IN 46202, USA
  • 6Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, 1044 W. Walnut St., Indianapolis, IN 46202, USA
  • 7Indiana University Simon Comprehensive Cancer Center, Indiana University School of Medicine, 1044 W. Walnut St., Indianapolis, IN 46202, USA
  • 8Eugene and Marilyn Glick Eye Institute, Department of Ophthalmology, Indiana University School of Medicine, 1044 W. Walnut St., Indianapolis, IN 46202, USA
+ Affiliations - Affiliations

Corresponding Author

Prof. Mark R. Kelley, mkelley@iu.edu

Received Date: May 11, 2021

Accepted Date: June 25, 2021

Citation:

Heisel C, Yousif J, Mijiti M, Charizanis K, Brigell M, Corson TW, et al. APE1/Ref-1 as a Novel Target for Retinal Diseases. J Cell Signal. 2021;2(2):133-138.


Copyright: © 2021 Heisel C, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

APE1/Ref-1 (also called Ref-1) has been extensively studied for its role in DNA repair and reduction-oxidation (redox) signaling. The review titled: “The multifunctional APE1 DNA repair-redox signaling protein as a drug target in human disease” by Caston et. al. summarizes the molecular functions of Ref-1 and the role it plays in a number of diseases, with a specific focus on various types of cancer [1]. Previous studies have demonstrated that Ref-1 plays a critical role in regulating specific transcription factors (TFs) involved in a number of pathways, not only in cancer, but other disease indications as well. Disease indications of particular therapeutic interest include retinal vascular diseases such as diabetic retinopathy (DR), diabetic macular edema (DME), and neovascular agerelated macular degeneration (nvAMD). While Ref-1 controls a number of TFs that are under redox regulation, three have been found to directly link cancer studies to retinal diseases; HIF-1α, NF-κB and STAT3. HIF-1α controls the expression of VEGF for angiogenesis while NF-κB and STAT3 regulate a number of known cytokines and factors involved in inflammation. These pathways are highly implicated and validated as major players in DR, DME and AMD. Therefore, findings in cancer studies for Ref-1 and its inhibition may be translated to these ocular diseases. This report discusses the path from cancer to the potential treatment of retinal disease, the Ref-1 redox signaling function as a possible target, and the current small molecules which have been identified to block this activity. One molecule, APX3330, is in clinical trials, while the others are in preclinical development. Inhibition of Ref-1 and its effects on inflammation and angiogenesis makes it a potential new therapeutic target for the treatment of retinal vascular diseases. This commentary summarizes the retinal-relevant research that built on the results summarized in the review by Caston et. al. [1].

Keywords

Redox effector factor 1, Apurinic/apyrimidinic endonuclease, Redox signaling, APE1/Ref-1, Angiogenesis, Inflammation, Transcription factors, Ocular clinical trial, Retina, Choroid, Neovascularization

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