• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Life sciences >CEREBROVASCULAR TRANSPORT OF ALZHEIMERS AMYLOID BETA AND APOLIPOPROTEINS J AND E - POSSIBLE ANTI-AMYLOIDOGENIC ROLE OF THE BLOOD-BRAIN BARRIER [Review]
【24h】

CEREBROVASCULAR TRANSPORT OF ALZHEIMERS AMYLOID BETA AND APOLIPOPROTEINS J AND E - POSSIBLE ANTI-AMYLOIDOGENIC ROLE OF THE BLOOD-BRAIN BARRIER [Review]

机译：脑血管化淀粉样淀粉样蛋白和载脂蛋白J和E的脑血管运输-血脑屏障的可能的抗淀粉样蛋白作用[综述]

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

It is uncertain whether soluble circulating amyloid beta (sA beta) is the precursor of amyloid beta (A beta) found in cerebrovascular and parenchymal amyloid lesions in Alzheimer's Disease, and if so, how the transition to the filamentous form is brought about. Several lines of evidence suggest that apolipoprotein E (apoE) and apolipoprotein J (apoJ) may be involved in the regulation of amyloidogenesis. They both bind sA beta/A beta in vivo and in vitro. It has been suggested that apoE may modulate beta-pleated conformation of A beta and therefore act as a pro-amyloidogenic factor. On the other hand, apoJ as a major carrier protein of sA beta in body fluids may keep the peptide in a soluble form, thus having an anti-amyloidogenic effect. Using a well established guinea-pig brain perfusion model we have studied the blood-brain barrier (BBB) processes involved in the regulation of cerebral capillary sequestration, transport and metabolism of i) sA beta(1-40) and sA beta(1-42), synthetic peptides identical to the 40 and 42 residue forms of A beta, found primarily in vascular deposits and senile plaques, respectively; and ii) apoJ, apoE3 and apoE4 alone, and in a complex with sA beta. Specific saturable BBB luminal binding of both peptides was followed by transport into brain parenchyma and metabolism at the abluminal side of the BBB and/or in brain. The capillary sequestration of sA beta(1-40) was significant, while retention by the microvasculature of sA beta(1-42) was negligible. Binding to microvessels and blood-to-brain transport of both intact apoJ and sA beta(1-40)-apoJ complexes were among the highest ever recorded for peptides and proteins at the BBB in vivo. These processes appear to be mediated by glycoprotein 330 (gp330/megalin), a receptor for multiple ligands, including apoJ. In contrast, capillary retention and transport of apoE3, apoE4 and sA beta(1-40)-apoE3 complex were low to negligible, while blood-brain transport of sA beta(1-40)-apoE4 was moderate. It is suggested that normal BBB may have predominantly anti-amyloidogenic functions by i) degrading sA beta during blood-to-brain transport; ii) favoring sequestration and transport of apoJ alone and in complex with sA beta via gp330 receptor-mediated mechanism and iii) excluding apoE3 and apoE4 isoforms from brain. [References: 83]
机译：尚不清楚在阿尔茨海默氏病的脑血管和实质淀粉样蛋白病变中发现的可溶性循环淀粉样蛋白β（sA beta）是否是淀粉样蛋白β（A beta）的前体，如果是的话，如何实现向丝状形式的转变。有几条证据表明，载脂蛋白E（apoE）和载脂蛋白J（apoJ）可能参与淀粉样蛋白的调控。它们在体内和体外均结合sA beta / A beta。已经提出apoE可以调节Aβ的β折叠构象，因此充当促淀粉样蛋白形成因子。另一方面，apoJ作为体液中sAβ的主要载体蛋白，可以使肽保持可溶形式，因此具有抗淀粉样蛋白作用。使用建立良好的豚鼠脑灌注模型，我们研究了血脑屏障（BBB）过程，涉及i）sA beta（1-40）和sA beta（1-）的脑毛细管螯合，转运和代谢的调节42），与Aβ的40和42个残基形式相同的合成肽，分别主要存在于血管沉积物和老年斑中; ii）单独的apoJ，apoE3和apoE4，以及与sA beta形成的复合物。两种肽的特异性可饱和BBB腔结合，然后转运到脑实质中，并在BBB的腔侧和/或在大脑中代谢。 sA beta（1-40）的毛细管隔离是显着的，而sA beta（1-42）的微脉管系统的保留可以忽略不计。完整的apoJ和sA beta（1-40）-apoJ复合物与微血管的结合和血脑运输在BBB体内的肽和蛋白质记录中最高。这些过程似乎是由糖蛋白330（gp330 / megalin）介导的，糖蛋白330是包括apoJ在内的多个配体的受体。相反，apoE3，apoE4和sA beta（1-40）-apoE3复合物的毛细血管保留和转运低至可以忽略不计，而sA beta（1-40）-apoE4的血脑转运则中等。提示正常的血脑屏障可能主要具有抗淀粉样蛋白生成的功能，包括：i）在血脑运输过程中降解sA beta; ii）通过gp330受体介导的机制促进apoJ的螯合和转运，并与sA beta结合，并且iii）从大脑排除apoE3和apoE4亚型。 [参考：83]

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号