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Nature:microRNA-34可抑制衰老和神经退化

  1. microRNA-34
  2. 果蝇
  3. 神经退化
  4. 衰老

来源:生物谷 2012-02-24 22:01

衰老是神经退行性疾病发生和发展的重要因素之一,但其中的分子机制却不得而知。近日,美国宾夕法尼亚大学的研究人员发现,microRNA-34在果蝇中可抑制衰老相关疾病的发生。相关论文发表在近期的Nature杂志上。 Mir-34的缺失可使大脑加速衰老,甚至缩短寿命。而若mir-34表达上调,果蝇的寿命则会延长,并且由人多谷氨酰胺病变蛋白诱发的神经退化也得到缓解。

衰老是神经退行性疾病发生和发展的重要因素之一,但其中的分子机制却不得而知。近日,美国宾夕法尼亚大学的研究人员发现,microRNA-34在果蝇中可抑制衰老相关疾病的发生。相关论文发表在近期的Nature杂志上。

Mir-34的缺失可使大脑加速衰老,甚至缩短寿命。而若mir-34表达上调,果蝇的寿命则会延长,并且由人多谷氨酰胺病变蛋白诱发的神经退化也得到缓解。果蝇的Eip74EF基因是miR-34的一个靶标。

结果表明,microRNA可以沉默一些与神经退化有关的基因,miR-34就发挥着这样的作用。(生物谷Bioon.com)

The microRNA miR-34 modulates ageing and neurodegeneration in Drosophila

Nan Liu, Michael Landreh, Kajia Cao, Masashi Abe, Gert-Jan Hendriks, Jason R. Kennerdel Yongqing Zhu, Li-San Wang & Nancy M. Bonini

Human neurodegenerative diseases have the temporal hallmark of afflicting the elderly population. Ageing is one of the most prominent factors to influence disease onset and progression1, yet little is known about the molecular pathways that connect these processes. To understand this connection it is necessary to identify the pathways that functionally integrate ageing, chronic maintenance of the brain and modulation of neurodegenerative disease. MicroRNAs (miRNA) are emerging as critical factors in gene regulation during development; however, their role in adult-onset, age-associated processes is only beginning to be revealed. Here we report that the conserved miRNA miR-34 regulates age-associated events and long-term brain integrity in Drosophila, providing a molecular link between ageing and neurodegeneration. Fly mir-34 expression exhibits adult-onset, brain-enriched and age-modulated characteristics. Whereas mir-34 loss triggers a gene profile of accelerated brain ageing, late-onset brain degeneration and a catastrophic decline in survival, mir-34 upregulation extends median lifespan and mitigates neurodegeneration induced by human pathogenic polyglutamine disease protein. Some of the age-associated effects of miR-34 require adult-onset translational repression of Eip74EF, an essential ETS domain transcription factor involved in steroid hormone pathways. Our studies indicate that miRNA-dependent pathways may have an impact on adult-onset, age-associated events by silencing developmental genes that later have a deleterious influence on adult life cycle and disease, and highlight fly miR-34 as a key miRNA with a role in this process.

 

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