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Neuron :研究揭示脑部疾病治疗新靶点!确定了保护神经功能的新目标

2017-07-16 佚名 来宝网

OHSU Vollum研究所的科学家已经发现了一种在神经系统内传递信号的神经细胞线状部分的轴突变性中发挥关键作用的酶。所有神经退行性疾病都发生轴突损失,因此这一发现可以为治疗或预防广泛的脑部疾病开辟新的途径。

OHSU Vollum研究所的科学家已经发现了一种在神经系统内传递信号的神经细胞线状部分的轴突变性中发挥关键作用的酶。所有神经退行性疾病都发生轴突损失,因此这一发现可以为治疗或预防广泛的脑部疾病开辟新的途径。

研究小组发现Axendead酶或Axed酶在促进轴突自身破坏方面发挥了新的作用。他们发现,当Axed功能被阻止时,受伤的轴突不仅保持了其完整性,而且仍然能够在大脑的复杂电路中传输信号数周。他们的研究于7月5日在Neuron杂志上发表。

OHSU Vollum研究所所长Marc Freeman博士说:“如果您瞄准这一途径,您将有机会在各种创伤或损伤之后保留神经元的功能。 “这是一个非常有吸引力的治疗目标。”

Freeman在马萨诸塞大学医学院的神经生物学系进行了工作。他已经被招聘到领导Vollum研究所,对研究神经系统在分子水平上的工作进行了前沿的基础研究。

切除轴突或轴突切除术是研究神经变性的分子基础,因为它导致爆发性轴索变性的激活是一种简单的方法。在实验室,使用这种技术的研究人员可以很好的识别出原始退行性基因,特别是在果蝇——弗里曼的主要研究模式生物体中使用复杂的遗传方法时。果蝇与人类共享这些相同的途径。弗里曼实验室以前的工作确定了另一种酶,一种称为SARM的基因,这是一种首次显示激活一种导致轴突在损伤时分解的过程。

在目前的研究中,Freeman及其同事发现Axed在SARM的下游发挥作用,可以执行轴突变性,而令人惊讶的是,阻塞Axed提供的保护比SARM更强。

Freeman说:“在Axed功能被阻止的地方,我们没有什么可以做的。

Freeman认为,从进化角度来看,SARM和Axed功能在损伤后的外周神经系统中可能很重要,因为编程的轴突死亡可以有效地包装损伤的细胞材料以免除细胞的去除。因此,该过程清除了新的神经元过程再生,恢复组织和恢复功能的途径。

从治疗的角度来看,工作的目标是在分子水平上了解轴突是如何退化的,并阻止患者的这些途径来保护神经系统的功能。在许多神经系统损伤中,轴突不被切断,但被拉伸或压碎,这激活了SARM依赖性死亡程序并驱动轴突损失。在这些情况下,必须阻止SARM和Axed信号,以保护轴突完整性。同时,Freeman等人已经表明SARM依赖性信号通路也可以在包括青光眼,创伤性脑损伤和周围神经病变在内的神经变性疾病中驱动轴突损失。这表明一种古老而保守的轴突死亡信号通路被广泛激活以驱动轴突损失的概念。由于轴突损失是神经退行性疾病的普遍特征,似乎阻止该途径可能具有巨大的治疗效果。

Freeman说:“如果我们可以找到阻止它的方法,也许我们可以通过神经退行性疾病或其他神经创伤在许多患有轴突损伤的患者中保留功能。

原始出处:
Neukomm LJ, Burdett TC, Seeds AM,et al.Axon Death Pathways Converge on Axundead to Promote Functional and Structural Axon Disassembly.Neuron. 2017 Jul 5;95(1):78-91.e5. doi: 10.1016/j.neuron.2017.06.031.

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    2018-03-16 by2021
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    2017-07-18 lsndxfj
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  7. [GetPortalCommentsPageByObjectIdResponse(id=1982768, encodeId=5c661982e683f, content=<a href='/topic/show?id=89c4e06902e' target=_blank style='color:#2F92EE;'>#疾病治疗#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=70690, encryptionId=89c4e06902e, topicName=疾病治疗)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d64f419, createdName=qindq, createdTime=Sun Feb 04 16:19:00 CST 2018, time=2018-02-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2037406, encodeId=5f0d203e4069e, content=<a href='/topic/show?id=1af68515859' target=_blank style='color:#2F92EE;'>#脑部疾病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=85158, encryptionId=1af68515859, topicName=脑部疾病)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=35fc2500023, createdName=yanjie6253_56072842, createdTime=Thu Dec 07 10:19:00 CST 2017, time=2017-12-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1751846, encodeId=cfb61e518466b, content=<a href='/topic/show?id=9b6a12e0155' target=_blank style='color:#2F92EE;'>#Neuron#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12701, encryptionId=9b6a12e0155, topicName=Neuron)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c9c736410065, createdName=by2021, createdTime=Fri Mar 16 04:19:00 CST 2018, time=2018-03-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1288223, encodeId=436f12882232f, content=<a href='/topic/show?id=f10658e342d' target=_blank style='color:#2F92EE;'>#新靶点#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=58734, encryptionId=f10658e342d, topicName=新靶点)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=acc3210, createdName=lsndxfj, createdTime=Tue Jul 18 03:19:00 CST 2017, time=2017-07-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1422061, encodeId=7ef1142206191, content=<a href='/topic/show?id=e5f0e42224f' target=_blank style='color:#2F92EE;'>#神经功能#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=82, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=74222, encryptionId=e5f0e42224f, topicName=神经功能)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=85503680375, createdName=lhlxtx, createdTime=Tue Jul 18 03:19:00 CST 2017, time=2017-07-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1517369, encodeId=ec9d151e36922, content=<a href='/topic/show?id=817b64646b3' target=_blank style='color:#2F92EE;'>#治疗新靶点#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=64646, encryptionId=817b64646b3, topicName=治疗新靶点)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=251911073486, createdName=12498f1em11(暂无昵称), createdTime=Tue Jul 18 03:19:00 CST 2017, time=2017-07-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=222931, encodeId=cb1d222931e5, content=学习了,涨知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=89, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220115/46bcf39c32de4aa6b45c5f9d66c8ee77/6cb4a20c55bb4b7691122f47747bfca2.jpg, createdBy=9dad1662329, createdName=1ddf0692m34(暂无匿称), createdTime=Sun Jul 16 14:13:12 CST 2017, time=2017-07-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=222923, encodeId=996b22292343, content=学习,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=91, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyhb9xDeHojCicsdRdyC3XXdGk2ib9yLypZuHN06WeW4HO8WN0GGrgEfvnTX8gsckof05GHOU5OM4Mvx/0, createdBy=9cee1982656, createdName=执着追梦, createdTime=Sun Jul 16 13:30:05 CST 2017, time=2017-07-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=222918, encodeId=3729222918ec, content=靶向治疗,更有针对性, beContent=null, objectType=article, channel=null, level=null, likeNumber=89, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://q.qlogo.cn/qqapp/1103841572/C3426ED027FF661B0C576A5B3127C2E8/40, createdBy=39dc1706090, createdName=QQ25ed180f, createdTime=Sun Jul 16 13:23:22 CST 2017, time=2017-07-16, status=1, ipAttribution=)]
    2017-07-16 1ddf0692m34(暂无匿称)

    学习了,涨知识

    0

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    2017-07-16 执着追梦

    学习,谢谢分享

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    2017-07-16 QQ25ed180f

    靶向治疗,更有针对性

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