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Science:研究人员识别新的C9orf72-相关ALS蛋白质靶点

2016-08-15 渐冻人尘雾 生物谷

在最新发表于《Science》的研究中,科学家们发现:以被称为SUPT4H1的单个蛋白质为靶点,能够减少C9orf72基因扩张所创造的三种毒性实体的水平。这一发现暗示,SUPT4H1可能作为有前途的候选者,为C9orf72基因导致的肌萎缩侧索硬化症(ALS)患者开发疗法。这项研究由美国ALS协会支持,由梅奥诊所Leonard Petrucelli博士和斯坦福大学Aaron Gitler博士领导

在最新发表于《Science》的研究中,科学家们发现:以被称为SUPT4H1的单个蛋白质为靶点,能够减少C9orf72基因扩张所创造的三种毒性实体的水平。这一发现暗示,SUPT4H1可能作为有前途的候选者,为C9orf72基因导致的肌萎缩侧索硬化症(ALS)患者开发疗法。这项研究由美国ALS协会支持,由梅奥诊所Leonard Petrucelli博士和斯坦福大学Aaron Gitler博士领导,其他共同领导的研究人员包括:Nicholas Kramer博士、Yari Carlomagno博士、Fen-Biao Gao博士和Yong-Jie Zhang博士。

ALS也被称为卢伽雷氏症,是一种侵犯大脑和脊髓中神经细胞的进行性神经退行性疾病。最终,ALS患者会失去发起和控制肌肉活动的能力,导致完全瘫痪和死亡。该病目前尚无治愈或有效治疗方法。

C9orf72基因扩张包含很长的六核苷酸序列(GGGGCC)重复。扩张会导向产生两种不同的RNA分子(称为“正义”和“反义”转录),以及多种被称为二肽重复蛋白(DPRs)的不寻常蛋白质。证据表明,两种转录物和DPRs都会导致毒性,目前正在开发治疗方法以减少它们(的水平)。

新的研究调查了减少酵母转录因子Spt4(人类中被称为SUPT4H1)的影响。转录因子控制RNA从基因的产生,具体到Spt4,它控制长的(而非短的)重复基因区域的伸长(elongation)。因此,论文作者们认为:减少Spt4可能减少突变基因长扩张区域的表达,而不影响非扩张基因(C9orf72基因扩张导致的ALS患者也携带一个正常非扩张基因)。

他们发现,减少酵母中的Spt4数量,能够同时减少来自C9orf92扩张基因的正义和反义转录物以及DPRs的数量,但不影响来自非扩张基因的转录物水平。在果蝇和蠕虫C9orf72突变模型中,研究人员看到了相似的结果,治疗还改善了生存状况。在源于ALS患者的人类细胞中,减少SUPT4H1也具有相似的效果,而且没有明显的毒性迹象。

“这项研究凸显了一个潜在重要的疗法开发新靶点”ALS协会首席科学家Lucie Bruijn博士说,“当前通过反义疗法来减少扩张C9orf72基因表达的工作将继续进行,我们对这种方法的前景感到非常兴奋。但与此同时,必须尽一切努力开发其他有前途的方法,新的研究结果暗示,以SUPT4H1为靶点可能为C9orf72基因突变导致的ALS提供新的和强大的治疗途径。”

原始出处

Spt4 selectively regulates the expression ofC9orf72?sense and antisense mutant transcripts

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encodeId=a290992e564, content=继续学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=84, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzfPkmqRTH5rHib5mcib8Wb3QdXjhfOK1UubQL2lictjJFdFJ6Lc3cnnCOSWqxXZ4Kk6y5GdzDoy764R/0, createdBy=156e1644785, createdName=doctorJiangchao, createdTime=Tue Aug 16 15:52:00 CST 2016, time=2016-08-16, status=1, ipAttribution=)]
    2016-08-18 1dd8a7c5m95(暂无匿称)

    学习了,赞一个!

    0

  4. 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encodeId=a290992e564, content=继续学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=84, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzfPkmqRTH5rHib5mcib8Wb3QdXjhfOK1UubQL2lictjJFdFJ6Lc3cnnCOSWqxXZ4Kk6y5GdzDoy764R/0, createdBy=156e1644785, createdName=doctorJiangchao, createdTime=Tue Aug 16 15:52:00 CST 2016, time=2016-08-16, status=1, ipAttribution=)]
    2016-08-18 1dd8a7c5m95(暂无匿称)

    学习了,赞一个!

    0

  5. 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encodeId=a290992e564, content=继续学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=84, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzfPkmqRTH5rHib5mcib8Wb3QdXjhfOK1UubQL2lictjJFdFJ6Lc3cnnCOSWqxXZ4Kk6y5GdzDoy764R/0, createdBy=156e1644785, createdName=doctorJiangchao, createdTime=Tue Aug 16 15:52:00 CST 2016, time=2016-08-16, status=1, ipAttribution=)]
    2016-08-18 1dd8a7c5m95(暂无匿称)

    学习了,赞一个!

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=1765590, encodeId=060c1e655906a, content=<a href='/topic/show?id=252ae1803a3' target=_blank style='color:#2F92EE;'>#白质#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=86, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=71803, encryptionId=252ae1803a3, topicName=白质)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=778d36, createdName=柳叶一刀, createdTime=Tue Aug 01 11:09:00 CST 2017, time=2017-08-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1907454, encodeId=ebc7190e454b2, content=<a href='/topic/show?id=379fe3364c9' target=_blank style='color:#2F92EE;'>#研究人员#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=73364, encryptionId=379fe3364c9, topicName=研究人员)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=db5b227, 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beContent=null, objectType=article, channel=null, level=null, likeNumber=78, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15998, encryptionId=2949159989d, topicName=SCIE)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=17a3387, createdName=jichang, createdTime=Wed Aug 17 08:09:00 CST 2016, time=2016-08-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1426286, encodeId=4b2f142628695, content=<a href='/topic/show?id=0eba392457' target=_blank style='color:#2F92EE;'>#C9orf72#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=74, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3924, encryptionId=0eba392457, topicName=C9orf72)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=683d4051559, createdName=cmsvly, createdTime=Wed Aug 17 08:09:00 CST 2016, time=2016-08-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=99275, encodeId=a290992e564, content=继续学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=84, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzfPkmqRTH5rHib5mcib8Wb3QdXjhfOK1UubQL2lictjJFdFJ6Lc3cnnCOSWqxXZ4Kk6y5GdzDoy764R/0, createdBy=156e1644785, createdName=doctorJiangchao, createdTime=Tue Aug 16 15:52:00 CST 2016, time=2016-08-16, status=1, ipAttribution=)]
    2016-08-17 忠诚向上

    好好学习一下

    0

  7. 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createdName=gostraight, createdTime=Mon Apr 17 01:09:00 CST 2017, time=2017-04-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=100444, encodeId=0d5810044465, content=学习了,赞一个!, beContent=null, objectType=article, channel=null, level=null, likeNumber=132, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=ebe61630855, createdName=1dd8a7c5m95(暂无匿称), createdTime=Thu Aug 18 17:42:00 CST 2016, time=2016-08-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=100445, encodeId=aa8410044596, content=学习了,赞一个!, beContent=null, objectType=article, channel=null, level=null, likeNumber=108, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, 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likeNumber=191, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=45101626056, createdName=忠诚向上, createdTime=Wed Aug 17 12:30:00 CST 2016, time=2016-08-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1296937, encodeId=18f9129693eb3, content=<a href='/topic/show?id=158288e017c' target=_blank style='color:#2F92EE;'>#蛋白质#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=137, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88701, encryptionId=158288e017c, topicName=蛋白质)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c689267, createdName=cmj8wellington, createdTime=Wed Aug 17 08:09:00 CST 2016, time=2016-08-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1375317, encodeId=366c13e5317c7, content=<a href='/topic/show?id=2949159989d' target=_blank style='color:#2F92EE;'>#SCIE#</a>, 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encodeId=a290992e564, content=继续学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=84, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzfPkmqRTH5rHib5mcib8Wb3QdXjhfOK1UubQL2lictjJFdFJ6Lc3cnnCOSWqxXZ4Kk6y5GdzDoy764R/0, createdBy=156e1644785, createdName=doctorJiangchao, createdTime=Tue Aug 16 15:52:00 CST 2016, time=2016-08-16, status=1, ipAttribution=)]
  8. [GetPortalCommentsPageByObjectIdResponse(id=1765590, encodeId=060c1e655906a, content=<a href='/topic/show?id=252ae1803a3' target=_blank style='color:#2F92EE;'>#白质#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=86, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=71803, encryptionId=252ae1803a3, topicName=白质)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=778d36, createdName=柳叶一刀, createdTime=Tue Aug 01 11:09:00 CST 2017, time=2017-08-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1907454, encodeId=ebc7190e454b2, content=<a href='/topic/show?id=379fe3364c9' target=_blank style='color:#2F92EE;'>#研究人员#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=73364, encryptionId=379fe3364c9, topicName=研究人员)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=db5b227, 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likeNumber=191, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=45101626056, createdName=忠诚向上, createdTime=Wed Aug 17 12:30:00 CST 2016, time=2016-08-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1296937, encodeId=18f9129693eb3, content=<a href='/topic/show?id=158288e017c' target=_blank style='color:#2F92EE;'>#蛋白质#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=137, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88701, encryptionId=158288e017c, topicName=蛋白质)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c689267, createdName=cmj8wellington, createdTime=Wed Aug 17 08:09:00 CST 2016, time=2016-08-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1375317, encodeId=366c13e5317c7, content=<a href='/topic/show?id=2949159989d' target=_blank style='color:#2F92EE;'>#SCIE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=78, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15998, encryptionId=2949159989d, topicName=SCIE)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=17a3387, createdName=jichang, createdTime=Wed Aug 17 08:09:00 CST 2016, time=2016-08-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1426286, encodeId=4b2f142628695, content=<a href='/topic/show?id=0eba392457' target=_blank style='color:#2F92EE;'>#C9orf72#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=74, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3924, encryptionId=0eba392457, topicName=C9orf72)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=683d4051559, createdName=cmsvly, createdTime=Wed Aug 17 08:09:00 CST 2016, time=2016-08-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=99275, encodeId=a290992e564, content=继续学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=84, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzfPkmqRTH5rHib5mcib8Wb3QdXjhfOK1UubQL2lictjJFdFJ6Lc3cnnCOSWqxXZ4Kk6y5GdzDoy764R/0, createdBy=156e1644785, createdName=doctorJiangchao, createdTime=Tue Aug 16 15:52:00 CST 2016, time=2016-08-16, status=1, ipAttribution=)]
    2016-08-17 jichang
  9. 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encodeId=a290992e564, content=继续学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=84, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzfPkmqRTH5rHib5mcib8Wb3QdXjhfOK1UubQL2lictjJFdFJ6Lc3cnnCOSWqxXZ4Kk6y5GdzDoy764R/0, createdBy=156e1644785, createdName=doctorJiangchao, createdTime=Tue Aug 16 15:52:00 CST 2016, time=2016-08-16, status=1, ipAttribution=)]
    2016-08-17 cmsvly
  10. 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likeNumber=191, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=45101626056, createdName=忠诚向上, createdTime=Wed Aug 17 12:30:00 CST 2016, time=2016-08-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1296937, encodeId=18f9129693eb3, content=<a href='/topic/show?id=158288e017c' target=_blank style='color:#2F92EE;'>#蛋白质#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=137, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88701, encryptionId=158288e017c, topicName=蛋白质)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c689267, createdName=cmj8wellington, createdTime=Wed Aug 17 08:09:00 CST 2016, time=2016-08-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1375317, encodeId=366c13e5317c7, content=<a href='/topic/show?id=2949159989d' target=_blank style='color:#2F92EE;'>#SCIE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=78, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15998, encryptionId=2949159989d, topicName=SCIE)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=17a3387, createdName=jichang, createdTime=Wed Aug 17 08:09:00 CST 2016, time=2016-08-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1426286, encodeId=4b2f142628695, content=<a href='/topic/show?id=0eba392457' target=_blank style='color:#2F92EE;'>#C9orf72#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=74, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3924, encryptionId=0eba392457, topicName=C9orf72)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=683d4051559, createdName=cmsvly, createdTime=Wed Aug 17 08:09:00 CST 2016, time=2016-08-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=99275, encodeId=a290992e564, content=继续学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=84, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzfPkmqRTH5rHib5mcib8Wb3QdXjhfOK1UubQL2lictjJFdFJ6Lc3cnnCOSWqxXZ4Kk6y5GdzDoy764R/0, createdBy=156e1644785, createdName=doctorJiangchao, createdTime=Tue Aug 16 15:52:00 CST 2016, time=2016-08-16, status=1, ipAttribution=)]
    2016-08-16 doctorJiangchao

    继续学习

    0

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