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JAD:中科院昆明动物所黄京飞组揭示帕金森病和阿茨海默病共同的NRF2/MAFF调节机制

2017-03-01 佚名 生物帮

昆明动物所中科院黄京飞调节机制阿茨海默病
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2017年2月20日，国际期刊《Journal of Alzheimer’s Disease》杂志在线发表了中国科学院昆明动物研究所黄京飞课题组的一篇研究论文，研究揭示帕金森病和阿茨海默病共同的NRF2/MAFF调节机制。



2017年2月20日，国际期刊《Journal of Alzheimer’s Disease》杂志在线发表了中国科学院昆明动物研究所黄京飞课题组的一篇研究论文，研究揭示帕金森病和阿茨海默病共同的NRF2/MAFF调节机制。黄京飞课题组的博士生王倩、研究生李文兴是本论文的共同第一作者。李功华副研究员和黄京飞研究员是论文的共同通讯作者。

神经退行性疾病是老年人最常见的疾病之一，其中两个典型代表是帕金森病 (Parkinson's disease(PD))和阿尔茨海默综合症(Alzheimer’s disease (AD)。PD和AD分别为两种不同类型的疾病，然而，越来越多的研究发现，PD和AD有许多相似的特征。例如，PD和AD都是与年龄相关的疾病；(2) PD和AD都有5%-10% 常染色体显性遗传；(3) PD和AD都有蛋白质聚合和包涵体形成的异常磷酸化的骨架；(4) PD和AD都显示线粒体功能障碍和氧化应激；(5)一些PD患者后期也患有有痴呆。

为进一步探究PD和AD这些共同的特征背后的分子机理，黄京飞课题组在NCBI-GEO和ArrayExpress数据库中筛选了9组PD相关的人类的基因芯片表达数据集和7组AD相关的数据集进行荟萃分析。分析结果表明PD和AD都在突出囊泡循环(synaptic vesicle cycle)、氨基丁酸能相关的突触(GABAergic synapses)， 吞噬体(phagosomes)， 氧化磷酸化(oxidative phosphorylation )和三羧酸循环(TCA cycle)代谢通路上有损伤，但是AD在每个通路上富集的基因更多。进一步研究发现AD和PD中共有54个相同的差异基因，其中31个下调基因上游序列都含有NRF2结合并调控的抗氧化应激区域(antioxidant response element (ARE))。NRF2是一个转录调控因子，在细胞处于氧化应激状态下，NRF2通过识别并结合到包含ARE序列基因的启动子上，调控这些抗氧化应激的基因表达，保护细胞免受氧化应激损伤。NRF2的转录调控作用与小MAFs的表达量相关，过量表达的小MAFs能够抑制NRF2的转录调控作用。研究发现，在AD和PD中尽管NRF2表达上调，31个包含ARE区域并由NRF2调控的靶基因却是下调的。进一步研究发现MAFF表达量几乎是NRF2的2倍而且MAFF和31个基因呈负相关。因此，结果表明MAFF在PD和AD疾病中与NRF2的转录调控作用失调密切相关。

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    2017-06-30 waiwai3030

    #黄京飞#

    0

  2. [GetPortalCommentsPageByObjectIdResponse(id=1822507, encodeId=fd2d182250e1a, content=<a href='/topic/show?id=946210310efc' target=_blank style='color:#2F92EE;'>#黄京飞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103107, encryptionId=946210310efc, topicName=黄京飞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=07f7192, createdName=waiwai3030, createdTime=Fri Jun 30 21:16:00 CST 2017, time=2017-06-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1862574, encodeId=07e118625e4d2, content=<a href='/topic/show?id=a121223385b' target=_blank style='color:#2F92EE;'>#中科院#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=22338, encryptionId=a121223385b, topicName=中科院)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7a9987, createdName=gous, createdTime=Wed Aug 30 20:16:00 CST 2017, time=2017-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1910919, encodeId=8db61910919ef, content=<a href='/topic/show?id=04d99206316' target=_blank style='color:#2F92EE;'>#调节机制#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=92063, encryptionId=04d99206316, topicName=调节机制)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=bf1b289, createdName=villahu, createdTime=Fri Apr 14 16:16:00 CST 2017, time=2017-04-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1407694, encodeId=dd6e140e6948f, content=<a href='/topic/show?id=7ee51303e38' target=_blank style='color:#2F92EE;'>#Nrf2#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13037, encryptionId=7ee51303e38, topicName=Nrf2)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c1842706563, createdName=minzju5053, createdTime=Fri Mar 03 11:16:00 CST 2017, time=2017-03-03, status=1, ipAttribution=)]
    2017-08-30 gous

    #中科院#

    0

  3. [GetPortalCommentsPageByObjectIdResponse(id=1822507, encodeId=fd2d182250e1a, content=<a href='/topic/show?id=946210310efc' target=_blank style='color:#2F92EE;'>#黄京飞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103107, encryptionId=946210310efc, topicName=黄京飞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=07f7192, createdName=waiwai3030, createdTime=Fri Jun 30 21:16:00 CST 2017, time=2017-06-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1862574, encodeId=07e118625e4d2, content=<a href='/topic/show?id=a121223385b' target=_blank style='color:#2F92EE;'>#中科院#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=22338, encryptionId=a121223385b, topicName=中科院)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7a9987, createdName=gous, createdTime=Wed Aug 30 20:16:00 CST 2017, time=2017-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1910919, encodeId=8db61910919ef, content=<a href='/topic/show?id=04d99206316' target=_blank style='color:#2F92EE;'>#调节机制#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=92063, encryptionId=04d99206316, topicName=调节机制)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=bf1b289, createdName=villahu, createdTime=Fri Apr 14 16:16:00 CST 2017, time=2017-04-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1407694, encodeId=dd6e140e6948f, content=<a href='/topic/show?id=7ee51303e38' target=_blank style='color:#2F92EE;'>#Nrf2#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13037, encryptionId=7ee51303e38, topicName=Nrf2)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c1842706563, createdName=minzju5053, createdTime=Fri Mar 03 11:16:00 CST 2017, time=2017-03-03, status=1, ipAttribution=)]
    2017-04-14 villahu

    #调节机制#

    0

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    2017-03-03 minzju5053

    #Nrf2#

    0