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Cell子刊:老年痴呆的致病蛋白,或许可以用于治疗癌症

2016-10-09 佚名 生物探索

导语:近期,《Developmental Cell》期刊发表一篇文章揭示,淀粉样蛋白可以让细胞进入休眠状态。当癌细胞中存储大量淀粉样蛋白时,它处于休眠状态。但是,热休克信号通路会降解这类蛋白,从而使得癌细胞“苏醒”,促使其增殖、扩散。对于阿尔兹海默症而言,淀粉样蛋白的存在通常是不好的预示,因为β-淀粉样蛋白是构成大脑老年斑的主要组成物质,是检测患病程度的重要指标之一,同时也是老年痴呆免疫疗法的关键

导语:近期,《Developmental Cell》期刊发表一篇文章揭示,淀粉样蛋白可以让细胞进入休眠状态。当癌细胞中存储大量淀粉样蛋白时,它处于休眠状态。但是,热休克信号通路会降解这类蛋白,从而使得癌细胞“苏醒”,促使其增殖、扩散。

对于阿尔兹海默症而言,淀粉样蛋白的存在通常是不好的预示,因为β-淀粉样蛋白是构成大脑老年斑的主要组成物质,是检测患病程度的重要指标之一,同时也是老年痴呆免疫疗法的关键靶标。

然而早在5月底,《Science Translational Medicine》期刊发表一篇文章为淀粉样蛋白“正名”,科学家们推测β-淀粉样蛋白或许还携带着一个古老的进化“使命”:保护大脑免于病原体的侵袭,功能类似于抗菌肽。(详细)

十月初,科学家对淀粉样蛋白又有了“好”的发现。来自于迈阿密大学米勒医学院的研究团队揭示,淀粉样蛋白可以让细胞,包括癌细胞,进入休眠状态。这或许可以为癌症治疗带来新范式,相关研究成果于10月6日发表在Cell子刊《Developmental Cell》上。

Stephen Lee博士带领研究团队发现了淀粉样蛋白的形成机制。超二级结构(motif)是蛋白质介于二级结构和三级结构之间的结构层次。淀粉样蛋白变性模体(ACM)能够通过与核糖体基因间隔区非编码RNA(rIGSRNA)互作,指引淀粉样蛋白的生成。β-淀粉样蛋白肽,有着类似于ACM的功能,能够介导细胞内淀粉样蛋白的沉积。在热休克信号通路上,其关键元素会降解淀粉样蛋白。



研究人员认为,这一机制是细胞应对压力的方式之一,能够让细胞存储大量的蛋白质,并进入休眠状态。淀粉样蛋白生成能够让细胞长期处于压力状态下维持活性。

休眠状态的癌细胞内会大量存储淀粉样蛋白,而热休克信号通路会降解沉积的淀粉样蛋白,使得癌细胞“苏醒”,从而促进其增殖、扩散。

Lee博士表示:“如果我们能够阻止癌细胞中淀粉样蛋白的降解,我们将有能力将癌变细胞永远维持在休眠状态。此外,我们或许还能够诱导活跃的癌细胞存储淀粉样蛋白,从而使其休眠。”这一新思路虽然不能消灭癌细胞,但是能够阻断癌症恶化。

原始出处:

Timothy E. Audas7, Danielle E. Audas, Mathieu D. Jacob, J.J. David Ho, Mireille Khacho, Miling Wang, J. Kishan Perera, Caroline Gardiner, Clay A. Bennett, Trajen Head, Oleksandr N. Kryvenko, Mercé Jorda, Sylvia Daunert, Arun Malhotra, Laura Trinkle-Mulcahy, Mark L. Gonzalgo, Stephen Lee8.Adaptation to Stressors by Systemic Protein Amyloidogenesis.Developmental Cell.2016.9

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    2017-03-16 维他命
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    2016-10-12 右脚梅西

    很好很有帮助谢谢。

    0

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    2016-10-11 1e10c84am36(暂无匿称)

    好文章,受益

    0

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    2016-10-10 知难而进

    继续关注!

    0

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    2016-10-10 知难而进

    谢谢分享!

    0

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    2016-10-10 meiliwuxian

    拭目以待

    0

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    2016-10-10 1e10c84am36(暂无匿称)

    文章很好,继续关注

    0

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    2016-10-09 boc_111

    这是个新思路,阻止淀粉样蛋白降解

    0

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