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JCI:抑制一种与痴呆相关的酶,或可逆转糖尿病患者的血管损伤

2020-07-01 转化医学网 转化医学网

英国一流顶尖大学利兹大学和邓迪大学的科学家发现了一项新突破,发现开发用于治疗阿尔茨海默氏病的药物,可以重新用于预防甚至逆转肥胖或患有2型糖尿病的人的血管损伤。该发现发表在《临床研究杂志》上,是八年来

BACE1(β-分泌酶1),又称为淀粉蛋白前β-分解酶1。是在外周神经细胞中形成髓鞘的一种重要的天冬氨酸蛋白酶,是一种包含两个活性位点的跨膜蛋白,可以在细胞外形成二聚体。

BACE1与阿尔茨海默氏病的联系

阿尔茨海默病的发病原因目前还没有完全了解,但是有证据表明,当人体内开始过量生产BACE1的酶时,它就会开始产生一种叫做β淀粉样蛋白的蛋白质。而β淀粉样蛋白水平升高与血管,内皮表面层的损害有关。这破坏了血管的正常功能,导致高血压和动脉粥样硬化,即沿血管壁的斑块堆积。

研究发现,BACE1不止生成β-淀粉样蛋白,还能破坏细胞生成PKA(蛋白激酶A)功能所需的因子,而PKA在记忆生成中起到重要作用。由此看来淀粉蛋白前β-分解酶1是治疗阿尔兹海默病的重要因素。

因此BACE1已引起制药行业的关注,已开始开发BACE1抑制剂。但到目前为止,它们在解决阿尔茨海默氏症方面一直无效,而是可以治疗这类人群的血管疾病。

抑制BACE1可逆转糖尿病患者的血管损伤

英国糖尿病患者协会的埃迪·约翰斯顿(Eddie Johnston)表示,糖尿病患者患心脏病或中风的风险较高,但尚不清楚确切的原因。这项新的研究有助于阐明这种联系。新疗法的有希望的目标,它可以帮助糖尿病患者更长寿,更健康。

这项研究涉及动物实验,其中研究了一种名为M-3的实验性化合物的作用,该化合物可终止BACE1的作用。在对肥胖或患有糖尿病的小鼠的研究中,它不仅可以阻止血管疾病,而且可以逆转疾病。

未用M-3的糖尿病小鼠的皮肤激光扫描图像。表明血液流动存在问题。蓝色表示血流量低。

接受M-3的M-3的糖尿病小鼠的皮肤激光扫描图像。显示出改善的血流。红黄绿代表较高的血流量。

论文的主要作者,利兹大学心血管与代谢医学研究所的大学学者保罗·梅金(Paul Meakin)博士。他表示,实验性化合物的治疗效果明显,严重受损血管中的疾病进展得以逆转。最令人兴奋的是,有一些药物可以靶向BACE1酶。它开辟了科学家开发抑制BACE1的药物的可能性,用证据表明,这些药物不仅可以阻止血管损伤,还可以逆转疾病。

邓迪大学神经科学教授迈克·阿什福德(Mike Ashford)监督了这项研究,他表明,与阿尔茨海默氏病密切相关的早期异常生物学过程,可能与肥胖和糖尿病患者的血管疾病和高血压有关。

英国心脏基金会副医学主任杰里米·皮尔森教授表示,糖尿病引起的血管损伤加速并加重了心脏和循环系统疾病。这些发现确定了一种新的破坏性途径,该途径已经被用于治疗阿尔茨海默氏病的药物开发。但用于抑制BACE1的药物还需在糖尿病患者中进行测试,它有潜力减缓英国数百万糖尿病患者的心脏和循环系统疾病的进展。

原始出处:

Paul J. Meakin, et al. Elevated circulating amyloid concentrations in obesity and diabetes promote vascular dysfunction. J Clin Invest. https://doi.org/10.1172/JCI122237.

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  5. [GetPortalCommentsPageByObjectIdResponse(id=1705712, encodeId=87ba1e05712c2, content=<a href='/topic/show?id=8e408966501' target=_blank style='color:#2F92EE;'>#血管损伤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=87, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=89665, encryptionId=8e408966501, topicName=血管损伤)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=84ba31025715, createdName=bbwuyu_013, createdTime=Wed Apr 07 13:07:50 CST 2021, time=2021-04-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1982124, encodeId=77c2198212444, content=<a href='/topic/show?id=12c010266f0' target=_blank style='color:#2F92EE;'>#JCI#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=65, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10266, encryptionId=12c010266f0, topicName=JCI)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5e30378, createdName=caobinglei8079, createdTime=Mon Jan 11 19:07:50 CST 2021, time=2021-01-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1397998, encodeId=97dd139e9987f, content=<a href='/topic/show?id=8bee565436d' target=_blank style='color:#2F92EE;'>#损伤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=56543, encryptionId=8bee565436d, topicName=损伤)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eoNX3lUOlDKGBUEPNwZx0nibmdcFyeibnX4WMhUSCU2REpGRWtSmnT2CCs0dA5waxvJknYDxwtYnIcQ/132, createdBy=294e2500218, createdName=ms3046638856685384, createdTime=Fri Jul 03 02:07:50 CST 2020, time=2020-07-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1474949, encodeId=c6dc14e4949e8, content=<a href='/topic/show?id=935fe6718e3' target=_blank style='color:#2F92EE;'>#糖尿病患者#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76718, encryptionId=935fe6718e3, topicName=糖尿病患者)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a38f7243741, createdName=xue8604, createdTime=Fri Jul 03 02:07:50 CST 2020, time=2020-07-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1043197, encodeId=bcf5104319e2f, content=谢谢MedSci提供最新的资讯, beContent=null, objectType=article, channel=null, level=null, likeNumber=65, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=misszhang, createdTime=Wed Jul 01 14:07:50 CST 2020, time=2020-07-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1048631, encodeId=0b1e1048631e9, content=老年人痴呆何药可用??, beContent=null, objectType=article, channel=null, level=null, likeNumber=96, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=junJUN, createdTime=Wed Jul 01 14:07:50 CST 2020, time=2020-07-01, status=1, ipAttribution=)]
    2020-07-01 misszhang

    谢谢MedSci提供最新的资讯

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=1705712, encodeId=87ba1e05712c2, content=<a href='/topic/show?id=8e408966501' target=_blank style='color:#2F92EE;'>#血管损伤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=87, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=89665, encryptionId=8e408966501, topicName=血管损伤)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=84ba31025715, createdName=bbwuyu_013, createdTime=Wed Apr 07 13:07:50 CST 2021, time=2021-04-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1982124, encodeId=77c2198212444, content=<a href='/topic/show?id=12c010266f0' target=_blank style='color:#2F92EE;'>#JCI#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=65, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10266, encryptionId=12c010266f0, topicName=JCI)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5e30378, createdName=caobinglei8079, createdTime=Mon Jan 11 19:07:50 CST 2021, time=2021-01-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1397998, encodeId=97dd139e9987f, content=<a href='/topic/show?id=8bee565436d' target=_blank style='color:#2F92EE;'>#损伤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=56543, encryptionId=8bee565436d, topicName=损伤)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eoNX3lUOlDKGBUEPNwZx0nibmdcFyeibnX4WMhUSCU2REpGRWtSmnT2CCs0dA5waxvJknYDxwtYnIcQ/132, createdBy=294e2500218, createdName=ms3046638856685384, createdTime=Fri Jul 03 02:07:50 CST 2020, time=2020-07-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1474949, encodeId=c6dc14e4949e8, content=<a href='/topic/show?id=935fe6718e3' target=_blank style='color:#2F92EE;'>#糖尿病患者#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76718, encryptionId=935fe6718e3, topicName=糖尿病患者)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a38f7243741, createdName=xue8604, createdTime=Fri Jul 03 02:07:50 CST 2020, time=2020-07-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1043197, encodeId=bcf5104319e2f, content=谢谢MedSci提供最新的资讯, beContent=null, objectType=article, channel=null, level=null, likeNumber=65, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=misszhang, createdTime=Wed Jul 01 14:07:50 CST 2020, time=2020-07-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1048631, encodeId=0b1e1048631e9, content=老年人痴呆何药可用??, beContent=null, objectType=article, channel=null, level=null, likeNumber=96, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=junJUN, createdTime=Wed Jul 01 14:07:50 CST 2020, time=2020-07-01, status=1, ipAttribution=)]
    2020-07-01 junJUN

    老年人痴呆何药可用??

    0

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