Stress-activated cap'n'collar transcription factors in aging and human disease.
Stress-activated cap'n'collar transcription factors in aging and human disease.
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DOI：
10.1126/scisignal.3112re3
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发表时间：
2010-03-09
影响因子：
7.3
通讯作者：
Bohmann D
中科院分区：
文献类型：
--
作者：
Sykiotis GP;Bohmann D
帽环（Cnc）转录因子在后生动物中是保守的，并且具有重要的发育和稳态功能。脊椎动物Nrf1、Nrf2和Nrf3、秀丽隐杆线虫SKN-1和果蝇CncC组成了介导细胞应激适应性反应的Cnc因子亚组。研究最多的应激激活的Cnc因子是Nrf2，其协调细胞对氧化应激因子和亲电子异生物质的转录反应。在啮齿动物模型中，Nrf2的信号传导可以防御氧化应激和衰老相关疾病，如神经退行性疾病、呼吸系统疾病和癌症。在人类中，减少Nrf2丰度的多态性与皮肤、呼吸系统和消化道的各种病理学有关。除了预防啮齿动物和人类的疾病外，Cnc因子在无脊椎动物中具有延长寿命和抗衰老的功能。然而，尽管应激激活的Cnc因子具有促长寿和抗氧化作用，但它们的活性在衰老模型生物体和患有进展性呼吸系统疾病或神经变性的人类中矛盾地下降。我们回顾了跨物种的应激激活的Cnc因子的作用和调节，提出了所有报道的情况下，他们的活动是矛盾的衰老和疾病下降，并讨论了可能性，药理学恢复Nrf2信号可能是有用的预防和治疗与年龄有关的疾病。
Cap’n’collar (Cnc) transcription factors are conserved in metazoans and have important developmental and homeostatic functions. The vertebrate Nrf1, Nrf2, and Nrf3, the Caenorhabditis elegans SKN-1, and the Drosophila CncC comprise a subgroup of Cnc factors that mediate adaptive responses to cellular stress. The most studied stress-activated Cnc factor is Nrf2, which orchestrates the transcriptional response of cells to oxidative stressors and electrophilic xenobiotics. In rodent models, signaling by Nrf2 defends against oxidative stress and aging-associated disorders, such as neurodegeneration, respiratory diseases, and cancer. In humans, polymorphisms that decrease Nrf2 abundance have been associated with various pathologies of the skin, respiratory system, and digestive tract. In addition to preventing disease in rodents and humans, Cnc factors have lifespan-extending and anti-aging functions in invertebrates. However, despite the pro-longevity and antioxidant roles of stress-activated Cnc factors, their activity paradoxically declines in aging model organisms and in humans suffering from progressing respiratory disease or neurodegeneration. We review the roles and regulation of stress-activated Cnc factors across species, present all reported instances in which their activity is paradoxically decreased in aging and disease, and discuss the possibility that the pharmacological restoration of Nrf2 signaling may be useful in the prevention and treatment of age-related diseases.
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影响因子：
56.9
作者：
Bonifati, V;Rizzu, P;Heutink, P
通讯作者：
Heutink, P
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影响因子：
7.8
作者：
Bjorkoy, Geir;Lamark, Trond;Brech, Andreas;Outzen, Heidi;Perander, Maria;Overvatn, Aud;Stenmark, Harald;Johansen, Terje
通讯作者：
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影响因子：
4.5
作者：
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通讯作者：
Antebi A
DOI：
10.1073/pnas.0405775102
发表时间：
2005-02-22
影响因子：
11.1
作者：
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通讯作者：
Partridge, L
影响因子：
3.8
作者：
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通讯作者：
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