Maiese Kenneth, Chong Zhao Zhong, Shang Yan Chen
Division of Cellular and Molecular Cerebral Ischemia, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Trends Mol Med. 2008 May;14(5):219-27. doi: 10.1016/j.molmed.2008.03.002. Epub 2008 Apr 9.
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.
叉头转录因子具有一个“翼状螺旋”结构域，并调控从细胞寿命到细胞死亡等一系列过程。在O类哺乳动物叉头家族成员中，FoxO1、FoxO3a和FoxO4对于治疗包括衰老、癌症、糖尿病、不孕症、神经退行性变和免疫系统功能障碍在内的疾病具有至关重要的作用。然而，有观察表明叉头家族成员也可能影响临床应用，这引发了争议，并凸显了进一步明确这些转录因子所调控的整合细胞通路的必要性。在此，我们讨论了近期的进展，这些进展阐明了靶向FoxO蛋白的独特细胞通路和临床潜力，以开发新的治疗策略，并避免可能与其对患者护理的益处紧密相关的潜在陷阱。
