Study summary · research use only
FOXO transcription factors as therapeutic targets in human diseases
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
This review discusses forkhead box (FOX)O transcription factors and their role as therapeutic targets in human diseases, noting four mammalian members (FOXO1, FOXO3, FOXO4, FOXO6) that the authors describe as playing a role in cellular adaptation to stress. It states FOXO proteins act as context-dependent tumor suppressors, that their dysregulation has been implicated in several age-related diseases, and that FOXO3 has been established as a major gene for human longevity. The review covers recent advances in understanding FOXO regulation and function across pathological conditions, discusses strategies targeting FOXOs directly or via upstream regulators, and reviews clinical indications along with the potential and challenges of modulating FOXO activity for therapeutic purposes.
Abstract
Forkhead box (FOX)O proteins are transcription factors (TFs) with four members in mammals designated FOXO1, FOXO3, FOXO4, and FOXO6. FOXO TFs play a pivotal role in the cellular adaptation to diverse stress conditions. FOXO proteins act as context-dependent tumor suppressors and their dysregulation has been implicated in several age-related diseases. FOXO3 has been established as a major gene for human longevity. Accordingly, FOXO proteins have emerged as potential targets for the therapeutic development of drugs and geroprotectors. In this review, we provide an overview of the most recent advances in our understanding of FOXO regulation and function in various pathological conditions. We discuss strategies targeting FOXOs directly or by the modulation of upstream regulators, shedding light on the most promising intervention points. We also reveal the most relevant clinical indications and discuss the potential, trends, and challenges of modulating FOXO activity for therapeutic purposes.
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