晚期糖基化终末产物受体介导β淀粉样肽通过血脑屏障的转运并在脑内蓄积。
RAGE mediates amyloid-beta peptide transport across the blood-brain barrier and accumulation in brain.
作者信息
Deane Rashid, Du Yan Shi, Submamaryan Ram Kumar, LaRue Barbara, Jovanovic Suzana, Hogg Elizabeth, Welch Deborah, Manness Lawrence, Lin Chang, Yu Jin, Zhu Hong, Ghiso Jorge, Frangione Blas, Stern Alan, Schmidt Ann Marie, Armstrong Don L, Arnold Bernd, Liliensiek Birgit, Nawroth Peter, Hofman Florence, Kindy Mark, Stern David, Zlokovic Berislav
机构信息
Frank P. Smith Laboratories for Neurosurgery, Department of Neurosurgery and Division of Neurovascular Biology, Center for Aging and Developmental Biology, University of Rochester Medical Center, Rochester, New York 14642, USA.
出版信息
Nat Med. 2003 Jul;9(7):907-13. doi: 10.1038/nm890.
Amyloid-beta peptide (Abeta) interacts with the vasculature to influence Abeta levels in the brain and cerebral blood flow, providing a means of amplifying the Abeta-induced cellular stress underlying neuronal dysfunction and dementia. Systemic Abeta infusion and studies in genetically manipulated mice show that Abeta interaction with receptor for advanced glycation end products (RAGE)-bearing cells in the vessel wall results in transport of Abeta across the blood-brain barrier (BBB) and expression of proinflammatory cytokines and endothelin-1 (ET-1), the latter mediating Abeta-induced vasoconstriction. Inhibition of RAGE-ligand interaction suppresses accumulation of Abeta in brain parenchyma in a mouse transgenic model. These findings suggest that vascular RAGE is a target for inhibiting pathogenic consequences of Abeta-vascular interactions, including development of cerebral amyloidosis.
β淀粉样肽（Aβ）与脉管系统相互作用，以影响大脑中的Aβ水平和脑血流量，提供了一种放大Aβ诱导的细胞应激的方式，这种应激是神经元功能障碍和痴呆的基础。全身性Aβ输注以及对基因操作小鼠的研究表明，Aβ与血管壁中带有晚期糖基化终产物受体（RAGE）的细胞相互作用，导致Aβ穿过血脑屏障（BBB）转运，并导致促炎细胞因子和内皮素-1（ET-1）的表达，后者介导Aβ诱导的血管收缩。在小鼠转基因模型中，抑制RAGE-配体相互作用可抑制Aβ在脑实质中的积累。这些发现表明，血管RAGE是抑制Aβ-血管相互作用的致病后果（包括脑淀粉样变性发展）的一个靶点。
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