Impaired vascular-mediated clearance of brain amyloid beta in Alzheimer's disease: the role, regulation and restoration of LRP1.
Impaired vascular-mediated clearance of brain amyloid beta in Alzheimer's disease: the role, regulation and restoration of LRP1.
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DOI：
10.3389/fnagi.2015.00136
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发表时间：
2015
影响因子：
4.8
通讯作者：
Zlokovic BV
中科院分区：
文献类型：
--
作者：
Ramanathan A;Nelson AR;Sagare AP;Zlokovic BV
β淀粉样蛋白（Aβ）在大脑中的稳态是由其产生和清除机制控制的。这种体内平衡的不平衡导致大脑a β的病理积累，这是阿尔茨海默病（AD）的一个特征。虽然a β可能通过几种生理机制被清除，但a β清除的主要途径是血管介导的通过血脑屏障（BBB）从大脑中清除a β。在这里，我们讨论了主要的Aβ清除蛋白-低密度脂蛋白受体相关蛋白1 （LRP1）在Aβ从大脑外排中的作用。我们还概述了影响lrp1介导的Aβ清除功能的多种因素，如其表达、脱落、结构修饰和其他基因的转录调控。最后，我们总结了旨在恢复lrp1介导的大脑Aβ清除的方法。
Amyloid beta (Aβ) homeostasis in the brain is governed by its production and clearance mechanisms. An imbalance in this homeostasis results in pathological accumulations of cerebral Aβ, a characteristic of Alzheimer’s disease (AD). While Aβ may be cleared by several physiological mechanisms, a major route of Aβ clearance is the vascular-mediated removal of Aβ from the brain across the blood-brain barrier (BBB). Here, we discuss the role of the predominant Aβ clearance protein—low-density lipoprotein receptor-related protein 1 (LRP1)—in the efflux of Aβ from the brain. We also outline the multiple factors that influence the function of LRP1-mediated Aβ clearance, such as its expression, shedding, structural modification and transcriptional regulation by other genes. Finally, we summarize approaches aimed at restoring LRP1-mediated Aβ clearance from the brain.