Cell Rep:阿尔茨海默病中,凋亡蛋白caspase与Aβ诱导的突触丧失有关

2020-07-06 MedSci原创 MedSci原创

Aβ诱导突触损伤的机制之一与淀粉样β前体蛋白(APP)在D664位点被caspase切割,释放出可能具有细胞毒性的C31肽有关。

已有的研究显示,淀粉样蛋白β蛋白(Aβ)的毒性作用可能在阿尔茨海默病(AD)的发病机制中起着开创性的作用。然而,至今为止,我们对于Aβ如何导致突触功能障碍和突触丧失仍不清楚。

研究人员推测,Aβ诱导突触损伤的机制之一与淀粉样β前体蛋白(APP)在D664位点被caspase切割,释放出可能具有细胞毒性的C31肽有关。

在来自敲入APP基因突变(APP D664A),以抑制caspase切割的小鼠器官型片培养物中,Aβ诱导的突触损伤在两种Aβ毒性模型中明显减少。在用caspase抑制剂处理的小鼠中,突触的损失也被减弱。

重要的是,时间依赖性的突触丢失与caspase-3的局部激活相关,但在APP D664A培养物中不存在。

因此,研究人员提出,在Aβ诱导的突触损伤中,APP胞质区域在局部caspase激活介导的损伤途径中起着至关重要的作用。

 

原始出处:

Goonho Park et al. Caspase Activation and Caspase-Mediated Cleavage of APP Is Associated with Amyloid β-Protein-Induced Synapse Loss in Alzheimer’s Disease. Cell Reports (2020). DOI:https://doi.org/10.1016/j.celrep.2020.107839

 

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    2020-10-11 维他命
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createdBy=c3ff68, createdName=维他命, createdTime=Sun Oct 11 04:21:50 CST 2020, time=2020-10-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1817005, encodeId=a81d181e005c5, content=<a href='/topic/show?id=17b59e77626' target=_blank style='color:#2F92EE;'>#阿尔茨#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97776, encryptionId=17b59e77626, topicName=阿尔茨)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/Bnia2EtH2IvyBtniaWHPQOYAicsN3IAL1ZuPV7qyALcdCiawRJdEiafMxWTxzERQW7eeKg8HfCKCRK2CJicy073C4RJg/132, createdBy=464b2500186, createdName=ms1948154235210413, createdTime=Wed Sep 16 12:21:50 CST 2020, time=2020-09-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2055192, encodeId=4f4d205519278, content=<a href='/topic/show?id=091688615da' target=_blank style='color:#2F92EE;'>#蛋白C#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88615, encryptionId=091688615da, topicName=蛋白C)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4f2c2500194, createdName=446798725_87912765, createdTime=Wed May 12 16:21:50 CST 2021, time=2021-05-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1989452, encodeId=2c6d198945259, content=<a href='/topic/show?id=7033165e692' target=_blank style='color:#2F92EE;'>#SpA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=16576, encryptionId=7033165e692, topicName=SpA)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=db5b227, createdName=gostraight, createdTime=Tue Sep 29 20:21:50 CST 2020, time=2020-09-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2034019, encodeId=8dff203401943, content=<a href='/topic/show?id=b8d74135dd' target=_blank style='color:#2F92EE;'>#Caspase#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4135, encryptionId=b8d74135dd, topicName=Caspase)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ca20190, createdName=wushaoling, createdTime=Fri Jul 31 12:21:50 CST 2020, time=2020-07-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1871833, encodeId=609018e18334c, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Sat Jan 09 15:21:50 CST 2021, time=2021-01-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1470382, encodeId=825514e038215, content=<a href='/topic/show?id=45a79e7788c' target=_blank style='color:#2F92EE;'>#阿尔茨海默#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97778, encryptionId=45a79e7788c, topicName=阿尔茨海默)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c5917090900, createdName=yhj-time, createdTime=Wed Jul 08 02:21:50 CST 2020, time=2020-07-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1478795, encodeId=213114e87951f, content=<a href='/topic/show?id=76efe555021' target=_blank style='color:#2F92EE;'>#突触#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=75550, encryptionId=76efe555021, topicName=突触)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c5207457717, createdName=ms691033630344116, createdTime=Wed Jul 08 02:21:50 CST 2020, time=2020-07-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1605267, encodeId=77d3160526e6b, content=<a href='/topic/show?id=b820309108' target=_blank style='color:#2F92EE;'>#Aβ#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3091, encryptionId=b820309108, topicName=Aβ)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ee1c19366172, createdName=膀胱癌, createdTime=Wed Jul 08 02:21:50 CST 2020, time=2020-07-08, status=1, ipAttribution=)]
  5. [GetPortalCommentsPageByObjectIdResponse(id=1818028, encodeId=1c8b181802832, content=<a href='/topic/show?id=4c9f9e777ac' target=_blank style='color:#2F92EE;'>#阿尔茨海#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97777, encryptionId=4c9f9e777ac, topicName=阿尔茨海)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=636e2500187, createdName=12498da4m32(暂无昵称), createdTime=Mon Mar 22 06:21:50 CST 2021, time=2021-03-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1962130, encodeId=d699196213041, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, 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=Sun Oct 11 04:21:50 CST 2020, time=2020-10-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1817005, encodeId=a81d181e005c5, content=<a href='/topic/show?id=17b59e77626' target=_blank style='color:#2F92EE;'>#阿尔茨#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97776, encryptionId=17b59e77626, topicName=阿尔茨)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/Bnia2EtH2IvyBtniaWHPQOYAicsN3IAL1ZuPV7qyALcdCiawRJdEiafMxWTxzERQW7eeKg8HfCKCRK2CJicy073C4RJg/132, createdBy=464b2500186, createdName=ms1948154235210413, createdTime=Wed Sep 16 12:21:50 CST 2020, time=2020-09-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2055192, encodeId=4f4d205519278, content=<a href='/topic/show?id=091688615da' target=_blank style='color:#2F92EE;'>#蛋白C#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88615, encryptionId=091688615da, topicName=蛋白C)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4f2c2500194, createdName=446798725_87912765, createdTime=Wed May 12 16:21:50 CST 2021, time=2021-05-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1989452, encodeId=2c6d198945259, content=<a href='/topic/show?id=7033165e692' target=_blank style='color:#2F92EE;'>#SpA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=16576, encryptionId=7033165e692, topicName=SpA)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=db5b227, createdName=gostraight, createdTime=Tue Sep 29 20:21:50 CST 2020, time=2020-09-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2034019, encodeId=8dff203401943, content=<a href='/topic/show?id=b8d74135dd' target=_blank style='color:#2F92EE;'>#Caspase#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4135, encryptionId=b8d74135dd, topicName=Caspase)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ca20190, createdName=wushaoling, createdTime=Fri Jul 31 12:21:50 CST 2020, time=2020-07-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1871833, encodeId=609018e18334c, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Sat Jan 09 15:21:50 CST 2021, time=2021-01-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1470382, encodeId=825514e038215, content=<a href='/topic/show?id=45a79e7788c' target=_blank style='color:#2F92EE;'>#阿尔茨海默#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97778, encryptionId=45a79e7788c, topicName=阿尔茨海默)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c5917090900, createdName=yhj-time, createdTime=Wed Jul 08 02:21:50 CST 2020, time=2020-07-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1478795, encodeId=213114e87951f, content=<a href='/topic/show?id=76efe555021' target=_blank style='color:#2F92EE;'>#突触#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=75550, encryptionId=76efe555021, topicName=突触)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c5207457717, createdName=ms691033630344116, createdTime=Wed Jul 08 02:21:50 CST 2020, time=2020-07-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1605267, encodeId=77d3160526e6b, content=<a href='/topic/show?id=b820309108' target=_blank style='color:#2F92EE;'>#Aβ#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3091, encryptionId=b820309108, topicName=Aβ)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ee1c19366172, createdName=膀胱癌, createdTime=Wed Jul 08 02:21:50 CST 2020, time=2020-07-08, status=1, ipAttribution=)]
    2020-09-29 gostraight
  6. [GetPortalCommentsPageByObjectIdResponse(id=1818028, encodeId=1c8b181802832, content=<a href='/topic/show?id=4c9f9e777ac' target=_blank style='color:#2F92EE;'>#阿尔茨海#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97777, encryptionId=4c9f9e777ac, topicName=阿尔茨海)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=636e2500187, createdName=12498da4m32(暂无昵称), createdTime=Mon Mar 22 06:21:50 CST 2021, time=2021-03-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1962130, encodeId=d699196213041, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, 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=Sun Oct 11 04:21:50 CST 2020, time=2020-10-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1817005, encodeId=a81d181e005c5, content=<a href='/topic/show?id=17b59e77626' target=_blank style='color:#2F92EE;'>#阿尔茨#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97776, encryptionId=17b59e77626, topicName=阿尔茨)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/Bnia2EtH2IvyBtniaWHPQOYAicsN3IAL1ZuPV7qyALcdCiawRJdEiafMxWTxzERQW7eeKg8HfCKCRK2CJicy073C4RJg/132, createdBy=464b2500186, createdName=ms1948154235210413, createdTime=Wed Sep 16 12:21:50 CST 2020, time=2020-09-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2055192, encodeId=4f4d205519278, content=<a href='/topic/show?id=091688615da' target=_blank style='color:#2F92EE;'>#蛋白C#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88615, encryptionId=091688615da, topicName=蛋白C)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4f2c2500194, createdName=446798725_87912765, createdTime=Wed May 12 16:21:50 CST 2021, time=2021-05-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1989452, encodeId=2c6d198945259, content=<a href='/topic/show?id=7033165e692' target=_blank style='color:#2F92EE;'>#SpA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=16576, encryptionId=7033165e692, topicName=SpA)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=db5b227, createdName=gostraight, createdTime=Tue Sep 29 20:21:50 CST 2020, time=2020-09-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2034019, encodeId=8dff203401943, content=<a href='/topic/show?id=b8d74135dd' target=_blank style='color:#2F92EE;'>#Caspase#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4135, encryptionId=b8d74135dd, topicName=Caspase)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ca20190, createdName=wushaoling, createdTime=Fri Jul 31 12:21:50 CST 2020, time=2020-07-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1871833, encodeId=609018e18334c, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Sat Jan 09 15:21:50 CST 2021, time=2021-01-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1470382, encodeId=825514e038215, content=<a href='/topic/show?id=45a79e7788c' target=_blank style='color:#2F92EE;'>#阿尔茨海默#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97778, encryptionId=45a79e7788c, topicName=阿尔茨海默)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c5917090900, createdName=yhj-time, createdTime=Wed Jul 08 02:21:50 CST 2020, time=2020-07-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1478795, encodeId=213114e87951f, content=<a href='/topic/show?id=76efe555021' target=_blank style='color:#2F92EE;'>#突触#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=75550, encryptionId=76efe555021, topicName=突触)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c5207457717, createdName=ms691033630344116, createdTime=Wed Jul 08 02:21:50 CST 2020, time=2020-07-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1605267, encodeId=77d3160526e6b, content=<a href='/topic/show?id=b820309108' target=_blank style='color:#2F92EE;'>#Aβ#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3091, encryptionId=b820309108, topicName=Aβ)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ee1c19366172, createdName=膀胱癌, createdTime=Wed Jul 08 02:21:50 CST 2020, time=2020-07-08, status=1, ipAttribution=)]
  7. [GetPortalCommentsPageByObjectIdResponse(id=1818028, encodeId=1c8b181802832, content=<a href='/topic/show?id=4c9f9e777ac' target=_blank style='color:#2F92EE;'>#阿尔茨海#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97777, encryptionId=4c9f9e777ac, topicName=阿尔茨海)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=636e2500187, createdName=12498da4m32(暂无昵称), createdTime=Mon Mar 22 06:21:50 CST 2021, time=2021-03-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1962130, encodeId=d699196213041, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, 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    2020-07-08 膀胱癌

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研究人员使用基因工程的人类诱导多能干细胞衍生的小胶质细胞样细胞发现,TREM2通过PLCγ2信号来介导细胞存活、吞噬能力、神经元碎片的处理和脂质代谢。

NEURON:研究人员绘制AD风险网络图谱

有证据表明,阿尔茨海默病(AD)的三大风险因素之间存在相互作用:年龄、APOE基因型和性别。

Lancet:唐氏综合征患者阿尔茨海默生物标志物特征研究

阿尔茨海默病在唐氏综合征患者中存在很长的临床前阶段,期间,生物标志物遵循一个可预测的变化顺序,长达20年

盘点:假期充电,阿尔兹海默症近期重要研究进展汇总

【1】阿尔兹海默危险基因APOE4破坏血脑屏障