Deciphering FOXO3: Functions, Regulation, and Implications in Disease and Therapy

This is the authors' abstract. We don't add key points for this paper.

Forkhead box O3 (FOXO3) is a critical transcription factor within the FOXO family that regulates various physiological and pathological processes, including metabolism, stress response, apoptosis, and cell cycle control. FOXO3 activity is primarily regulated by post-translational modifications, including phosphorylation, acetylation, and ubiquitination, while interacting with key pathways such as PI3K/Akt and AMPK. These pathways regulate FOXO3's localization and activity within cells, influencing processes like autophagy, oxidative stress resistance, and longevity. FOXO3 also plays a pivotal role in aging, cancer, metabolic regulation, and neurodegenerative diseases. Research highlights FOXO3’s dual role as a tumor suppressor and a contributor to cellular survival under stress, making it an essential target for therapeutic strategies. This review discusses the regulation, biological functions, and therapeutic potential of FOXO3 in various disease contexts.