Maiese Kenneth, Chong Zhao Zhong, Shang Yan Chen, Hou Jinling
Division of Cellular and Molecular Cerebral Ischemia, Department of Neurology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
Med Res Rev. 2009 May;29(3):395-418. doi: 10.1002/med.20139.
The successful treatment for multiple disease entities can rest heavily upon the ability to elucidate the intricate relationships that govern cellular proliferation, metabolism, survival, and inflammation. Here we discuss the therapeutic potential of the mammalian forkhead transcription factors predominantly in the O class, FoxO1, FoxO3, FoxO4, and FoxO6, which play a significant role during normal cellular function as well as during progressive disease. These transcription factors are integrated with several signal transduction pathways, such as Wnt proteins, that can regulate a broad array of cellular process that include stem cell proliferation, aging, and malignancy. FoxO transcription factors are attractive considerations for strategies directed against human cancer in light of their pro-apoptotic effects and ability to lead to cell cycle arrest. Yet, FoxO proteins can be associated with infertility, cellular degeneration, and unchecked cellular proliferation. As our knowledge continues to develop for this novel family of proteins, potential clinical applications for the FoxO family should heighten our ability to limit disease progression without clinical compromise.
多种疾病实体的成功治疗在很大程度上取决于阐明控制细胞增殖、代谢、存活和炎症的复杂关系的能力。在此，我们主要讨论哺乳动物叉头转录因子O类中的FoxO1、FoxO3、FoxO4和FoxO6的治疗潜力，它们在正常细胞功能以及疾病进展过程中发挥着重要作用。这些转录因子与多种信号转导途径整合在一起，如Wnt蛋白，可调节包括干细胞增殖、衰老和恶性肿瘤在内的广泛细胞过程。鉴于其促凋亡作用和导致细胞周期停滞的能力，FoxO转录因子是针对人类癌症策略的有吸引力的考虑因素。然而，FoxO蛋白可能与不孕症、细胞变性和不受控制的细胞增殖有关。随着我们对这个新的蛋白质家族的认识不断发展，FoxO家族的潜在临床应用应该会提高我们在不影响临床的情况下限制疾病进展的能力。
