OutFOXOing disease and disability: the therapeutic potential of targeting FoxO proteins.
Forkhead transcription factors have a 'winged helix' domain and regulate processes that range from cell longevity to cell death. Of the mammalian forkhead family members in the O class, FoxO1, FoxO3a and FoxO4 can fill a crucial void for the treatment of disorders that include aging, cancer, diabetes, infertility, neurodegeneration and immune system dysfunction. Yet, observations that forkhead family members also can compromise clinical utility have fueled controversy and highlight the necessity to further outline the integrated cellular pathways governed by these transcription factors. Here we discuss recent advances that have elucidated the unique cellular pathways and clinical potential of targeting FoxO proteins to develop novel therapeutic strategies and avert potential pitfalls that might be closely intertwined with its benefits for patient care.
Maiese
Kenneth
K
Division of Cellular and Molecular Cerebral Ischemia, Wayne State University School of Medicine, Detroit, MI 48201, USA. kmaiese@med.wayne.edu
Chong
Zhao Zhong
ZZ
Shang
Yan Chen
YC
D000818:Animals; D017209:Apoptosis; D018797:Cell Cycle Proteins; D002465:Cell Movement; D015195:Drug Design; D000071161:Forkhead Box Protein O1; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism / Q000628:therapy; D018384:Oxidative Stress; D021381:Protein Transport; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*
D018797:Cell Cycle Proteins; C085126:FOXO1 protein, human; C499517:FOXO3 protein, human; C108803:FOXO4 protein, human; D000071161:Forkhead Box Protein O1; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D014157:Transcription Factors