APE1/Ref-1 - One Target with Multiple Indications: Emerging Aspects and New Directions

Area of Science:

• Molecular Biology
• Biochemistry
• Genetics

Background:

• Apurinic/Apyrimidinic Endonuclease 1 (APE1/Ref-1) is a key DNA repair enzyme.
• Over the last decade, APE1 has emerged as a critical regulator in reduction-oxidation (redox) signaling pathways.
• Previous reviews have summarized APE1's roles, but recent findings highlight its broader involvement in disease.

Purpose of the Study:

• To expand upon the known roles of APE1 in various human diseases and its impact on disease progression.
• To explore novel functions of APE1 in cancer metabolism, chemotherapy-induced peripheral neuropathy (CIPN), inflammation, inflammatory bowel disease (IBD), and retinal ocular diseases.
• To discuss the therapeutic potential of APE1 redox inhibitors and examine APE1's role in RNA metabolism.

Main Methods:

• Literature review synthesizing recent research on APE1's multifaceted roles.
• Analysis of APE1's regulatory functions on transcription factors (TFs) and associated signaling pathways.
• Discussion of APE1 redox inhibitors as tools for disease research and potential therapeutic interventions.

Main Results:

• APE1 plays significant roles in cancer cell metabolism, CIPN, and inflammation.
• APE1 signaling is implicated in IBD and emerging as a focus in retinal diseases.
• APE1 regulates multiple TFs, influencing diverse pathways relevant to both cancer and non-cancerous diseases.

Conclusions:

• APE1 is a versatile protein with critical functions beyond DNA repair, particularly in redox signaling.
• Targeting APE1 offers a promising strategy for treating a range of diseases, including cancer and inflammatory conditions.
• Further investigation into APE1's role in RNA metabolism and its regulation of various pathways is warranted.