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Cell:抑制mtHSP70或有助治疗亨廷顿舞蹈病

2016-09-16 佚名 生物谷

在一项新的研究中,来自美国加州大学伯克利分校分子与细胞生物学系霍华德-休斯医学研究所研究员Andrew Dillin和他的同事们报道让大脑中的神经元遭受应激让它们释放一种被称作血清素(serotonin)的激素,其中这种激素给全身发出这些大脑细胞处于攻击中的警报信息,从而在离大脑较远处的细胞中发起一种类似的应激反应。在亨廷顿舞蹈病等疾病中,智力下降与外周代谢缺陷和肌肉变少相关联。相关研究结果发表在

在一项新的研究中,来自美国加州大学伯克利分校分子与细胞生物学系霍华德-休斯医学研究所研究员Andrew Dillin和他的同事们报道让大脑中的神经元遭受应激让它们释放一种被称作血清素(serotonin)的激素,其中这种激素给全身发出这些大脑细胞处于攻击中的警报信息,从而在离大脑较远处的细胞中发起一种类似的应激反应。在亨廷顿舞蹈病等疾病中,智力下降与外周代谢缺陷和肌肉变少相关联。相关研究结果发表在2016年9月8日那期Cell期刊上,论文标题为“Neuroendocrine Coordination of Mitochondrial Stress Signaling and Proteostasis”。

他说,“血清素释放显著地改变外周细胞和它们用作能量的来源的代谢输出,因此,我们认为它正在制定大规模的代谢重新布线(metabolic rewiring),从而可能保护大脑中的神经元。如果你开始关闭外周细胞,停止使用它利用的有限资源,那么更多的这些资源就能够转向大脑代谢活动。这可能是一种非常聪明的方法:试着通过让身体消瘦来拯救大脑。”

尽管Dillin几年前已发现线粒体能够在不同细胞和组织之间进行沟通,但是这项新研究精确鉴定出血清素是这种代谢反应的一种主要促进物。

Dillin注意到降低血清素水平的药物长期被用来治疗抑郁和神经退行性疾病的其他精神表征,但是这些新的发现提示着这些药物可能要比之前认为的更加广泛地用于治疗年龄相关性疾病。这些发现不仅对神经退行性疾病的潜在治疗而且也对进一步理解神经疾病在全身的代谢和应激反应中的影响产生广泛的影响。

线粒体是大脑退化的关键

作为细胞的能量工厂,线粒体不仅将营养物转化为能量,而且也在细胞信号、细胞死亡和生长中发挥着关键性作用。在过去几年,越来越多的证据已将线粒体功能障碍与衰老和阿尔茨海默病、帕金森病和亨廷顿舞蹈病等年龄发作性蛋白错误折叠疾病相关联。

尽管研究经过基因改造患上亨廷顿舞蹈病的线虫中的线粒体,但是Dillin和他的同事们发现这些异常的蛋白确实堆积在线粒体表面上,而且这会增加细胞内的蛋白折叠反应,这种折叠反应在线粒体中和细胞内部大量发生:将近100种所谓的热休克蛋白试图修复这些错误折叠的蛋白。这些热休克蛋白作为线粒体中的分子伴侣,辅助在线粒体外面合成的线粒体蛋白输入和折叠。

研究人员吃惊地发现抑制一种特异性的线粒体分子伴侣mtHSP70会引起脂肪堆积介导的一种独特的应激反应,从而导致细胞的内部或胞液中的蛋白折叠得到改善。激活这种新的应激反应通路---他们称之为线粒体到胞液应激反应---的药物保护患有亨廷顿舞蹈病的线虫和体外培养的人细胞免受蛋白折叠损伤。

他说,“可能有一种方法利用一种药物改变这种线粒体信号,和利用另一种药物来改变来自大脑中的这种通信信号。如果你在组织培养皿中研究蛋白折叠,那么你将从不会观察这两种影响,这是因为它没有研究整个秀丽隐杆线虫有机体,在那里,你能够研究通信信号。”

原始出处

Kristen M. Berendzen, Jenni Durieux3, Li-Wa Shao, Ye Tian, Hyun-eui Kim, Suzanne Wolff, Ying Liu, Andrew Dillin.Neuroendocrine Coordination of Mitochondrial Stress Signaling and Proteostasis.Cell.2016

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    2017-05-08 仁医06
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    2017-02-17 维他命
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  5. [GetPortalCommentsPageByObjectIdResponse(id=1975637, encodeId=00c719e563701, content=<a href='/topic/show?id=cf4824554d0' target=_blank style='color:#2F92EE;'>#亨廷顿舞蹈#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=24554, encryptionId=cf4824554d0, topicName=亨廷顿舞蹈)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e03212, createdName=liao1619, createdTime=Mon Feb 06 16:10:00 CST 2017, time=2017-02-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1869548, encodeId=598e18695485a, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=55683, createdName=仁医06, createdTime=Mon May 08 04:10:00 CST 2017, time=2017-05-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1959807, encodeId=c48d195980e5d, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Fri Feb 17 16:10:00 CST 2017, time=2017-02-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2069355, encodeId=647920693551b, content=<a href='/topic/show?id=f9cf2455528' target=_blank style='color:#2F92EE;'>#亨廷顿舞蹈病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=24555, encryptionId=f9cf2455528, topicName=亨廷顿舞蹈病)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=baf586, createdName=wangbingxhy, createdTime=Tue Jun 06 16:10:00 CST 2017, time=2017-06-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=129976, encodeId=62101299e64f, content=学习了,赞一个!!!, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, 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=Sun Sep 18 08:23:00 CST 2016, time=2016-09-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1622746, encodeId=79a01622e4688, content=<a href='/topic/show?id=4a6e2454879' target=_blank style='color:#2F92EE;'>#亨廷顿#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=24548, encryptionId=4a6e2454879, topicName=亨廷顿)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=395f25, createdName=爆笑小医, createdTime=Sun Sep 18 03:10:00 CST 2016, time=2016-09-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=129075, encodeId=a5ba1290e56c, content=很好的内容,继续学习。, beContent=null, objectType=article, channel=null, level=null, likeNumber=102, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ceb079804, createdName=lhl629, createdTime=Sat Sep 17 07:15:00 CST 2016, time=2016-09-17, status=1, ipAttribution=)]
    2016-09-18 1dd8a7c5m95(暂无匿称)

    学习了,赞一个!!!

    0

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  7. [GetPortalCommentsPageByObjectIdResponse(id=1975637, encodeId=00c719e563701, content=<a href='/topic/show?id=cf4824554d0' target=_blank style='color:#2F92EE;'>#亨廷顿舞蹈#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=24554, encryptionId=cf4824554d0, topicName=亨廷顿舞蹈)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e03212, createdName=liao1619, createdTime=Mon Feb 06 16:10:00 CST 2017, time=2017-02-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1869548, encodeId=598e18695485a, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=55683, createdName=仁医06, createdTime=Mon May 08 04:10:00 CST 2017, time=2017-05-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1959807, encodeId=c48d195980e5d, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Fri Feb 17 16:10:00 CST 2017, time=2017-02-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2069355, encodeId=647920693551b, content=<a href='/topic/show?id=f9cf2455528' target=_blank style='color:#2F92EE;'>#亨廷顿舞蹈病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=24555, encryptionId=f9cf2455528, topicName=亨廷顿舞蹈病)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=baf586, createdName=wangbingxhy, createdTime=Tue Jun 06 16:10:00 CST 2017, time=2017-06-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=129976, encodeId=62101299e64f, content=学习了,赞一个!!!, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, 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=Sun Sep 18 08:23:00 CST 2016, time=2016-09-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1622746, encodeId=79a01622e4688, content=<a href='/topic/show?id=4a6e2454879' target=_blank style='color:#2F92EE;'>#亨廷顿#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=24548, encryptionId=4a6e2454879, topicName=亨廷顿)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=395f25, createdName=爆笑小医, createdTime=Sun Sep 18 03:10:00 CST 2016, time=2016-09-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=129075, encodeId=a5ba1290e56c, content=很好的内容,继续学习。, beContent=null, objectType=article, channel=null, level=null, likeNumber=102, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ceb079804, createdName=lhl629, createdTime=Sat Sep 17 07:15:00 CST 2016, time=2016-09-17, status=1, ipAttribution=)]
    2016-09-17 lhl629

    很好的内容,继续学习。

    0

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