دورية أكاديمية
APE1/Ref-1 as a Novel Target for Retinal Diseases.
| العنوان: | APE1/Ref-1 as a Novel Target for Retinal Diseases. |
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| المؤلفون: | Heisel C; University of Michigan Medical School, 1301 Catherine St, Ann Arbor, MI 48105, USA., Yousif J; University of Michigan Medical School, 1301 Catherine St, Ann Arbor, MI 48105, USA., Mijiti M; Herman B Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, 1044 W. Walnut St., Indianapolis, IN 46202, USA., Charizanis K; Kostas Charizanis, Independent Consultant, Livonia, MI 48150, USA., Brigell M; Ocuphire Pharma Inc., Farmington Hills, MI, USA., Corson TW; Department of Pharmacology and Toxicology, Indiana University School of Medicine, 1044 W. Walnut St., Indianapolis, IN 46202, USA.; Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, 1044 W. Walnut St., Indianapolis, IN 46202, USA.; Indiana University Simon Comprehensive Cancer Center, Indiana University School of Medicine, 1044 W. Walnut St., Indianapolis, IN 46202, USA.; Eugene and Marilyn Glick Eye Institute, Department of Ophthalmology, Indiana University School of Medicine, 1044 W. Walnut St., Indianapolis, IN 46202, USA., Kelley MR; Herman B Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, 1044 W. Walnut St., Indianapolis, IN 46202, USA.; Department of Pharmacology and Toxicology, Indiana University School of Medicine, 1044 W. Walnut St., Indianapolis, IN 46202, USA.; Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, 1044 W. Walnut St., Indianapolis, IN 46202, USA.; Indiana University Simon Comprehensive Cancer Center, Indiana University School of Medicine, 1044 W. Walnut St., Indianapolis, IN 46202, USA.; Eugene and Marilyn Glick Eye Institute, Department of Ophthalmology, Indiana University School of Medicine, 1044 W. Walnut St., Indianapolis, IN 46202, USA. |
| المصدر: | Journal of cellular signaling [J Cell Signal] 2021; Vol. 2 (2), pp. 133-138. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Scientific Archives Country of Publication: United States NLM ID: 101767200 Publication Model: Print Cited Medium: Internet ISSN: 2692-0638 (Electronic) NLM ISO Abbreviation: J Cell Signal Subsets: PubMed not MEDLINE |
| أسماء مطبوعة: | Original Publication: Wilmington, DE : Scientific Archives, 2020- |
| مستخلص: | 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 age-related 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]. Competing Interests: Conflict of Interest CH and JY conducted internships at Ocuphire Pharma, KC is an independent consultant, MB is head of clinical development and strategy at Ocuphire Pharma and MRK is a member of the Ocuphire medical advisory board and CSO and co-founder of Apexian Pharmaceuticals which developed APX3330 for oncology. TWC and MRK are inventors on patent applications licensed to Ocuphire. MM has no conflicts. |
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| معلومات مُعتمدة: | R01 CA205166 United States CA NCI NIH HHS; R01 CA231267 United States CA NCI NIH HHS; R01 HL140961 United States HL NHLBI NIH HHS; R01 EY031939 United States EY NEI NIH HHS; R01 CA167291 United States CA NCI NIH HHS |
| فهرسة مساهمة: | Keywords: APE1/Ref-1; Angiogenesis; Apurinic/apyrimidinic endonuclease; Choroid; Inflammation; Neovascularization; Ocular clinical trial; Redox effector factor 1; Redox signaling; Retina; Transcription factors |
| تواريخ الأحداث: | Date Created: 20210729 Latest Revision: 20240607 |
| رمز التحديث: | 20240607 |
| مُعرف محوري في PubMed: | PMC8315574 |
| DOI: | 10.33696/Signaling.2.044 |
| PMID: | 34322687 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 2692-0638 |
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| DOI: | 10.33696/Signaling.2.044 |