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Oxidative Medicine and Cellular Longevity
Volume 2, Issue 3, Pages 119-129
http://dx.doi.org/10.4161/oxim.2.3.8916

A Fork in the Path: Developing Therapeutic Inroads with FoxO Proteins

1Division of Cellular and Molecular Cerebral Ischemia, Wayne State University School of Medicine, Detroit, MI, USA
2Departments of Neurology and Anatomy & Cell Biology, Wayne State University School of Medicine, Detroit, MI, USA
3Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USA
4Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI, USA
5Institute of Environmental Health Sciences, Wayne State University School of Medicine, Detroit, MI, USA

Received 6 April 2009; Revised 23 April 2009; Accepted 27 April 2009

Copyright © 2009 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Advances in clinical care for disorders involving any system of the body necessitates novel therapeutic strategies that can focus upon the modulation of cellular proliferation, metabolism, inflammation and longevity. In this respect, members of the mammalian forkhead transcription factors of the O class (FoxOs) that include FoxO1, FoxO3, FoxO4 and FoxO6 are increasingly being recognized as exciting prospects for multiple disorders. These transcription factors govern development, proliferation, survival and longevity during multiple cellular environments that can involve oxidative stress. Furthermore, these transcription factors are closely integrated with several novel signal transduction pathways, such as erythropoietin and Wnt proteins, that may influence the ability of FoxOs to act as a “double-edge sword” to sometimes promote cell survival, but at other times lead to cell injury. Here we discuss the fascinating but complex role of FoxOs during cellular injury and oxidative stress, progenitor cell development, fertility, angiogenesis, cardiovascular function, cellular metabolism and diabetes, cell longevity, immune surveillance and cancer.