Protection of the Blood-Brain Barrier by Pentosan Against Amyloid-β-Induced Toxicity
Protection of the Blood-Brain Barrier by Pentosan Against Amyloid-β-Induced Toxicity
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DOI：
10.3233/jad-2010-100759
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发表时间：
2010-01-01
影响因子：
4
通讯作者：
Niwa, Masami
中科院分区：
文献类型：
--
作者：
Deli, Maria A.;Veszelka, Szilvia;Niwa, Masami
形成血脑屏障的脑毛细血管内皮细胞在阿尔茨海默病的发病机制和治疗中发挥着重要作用。 β 淀粉样蛋白 (Aβ) 肽是该疾病发展的关键病理因素。使用基于原代大鼠脑内皮细胞的血脑屏障模型，其中屏障特性由神经胶质细胞诱导。淀粉样肽对细胞活力和屏障功能的影响已经过测试。通过 MTT 染料转化和乳酸脱氢酶释放测量，β 对原代大鼠脑内皮细胞显示出毒性作用。在脑内皮细胞中可以观察到形态上的细胞质空泡化、细胞质细胞器结构的破坏和紧密连接。 A beta(1-42) 治疗降低了电阻，并增加了脑内皮细胞单层对荧光素和白蛋白的通透性。血清淀粉样蛋白 P 成分可稳定皮质淀粉样斑块和脑血管淀粉样蛋白沉积物中的 Aβ 原纤维，显着增强 Aβ(1-42) 的屏障削弱作用。硫酸化多糖戊聚糖可降低Aβ肽对脑内皮细胞的毒性作用。它还可以显着保护单层屏障的完整性免受肽的破坏作用。戊聚糖改变了尺寸，并显着减少了原子力显微镜显示的淀粉样蛋白聚集体的数量。目前的数据进一步支持淀粉样肽对脑内皮细胞的毒性作用，并有助于开发保护阿尔茨海默病血脑屏障的分子。
Endothelial cells of brain capillaries forming the blood-brain barrier play an important role in the pathogenesis and therapy of Alzheimer's disease. Amyloid-beta (A beta) peptides are key pathological elements in the development of the disease. A blood-brain barrier model, based on primary rat brain endothelial cells was used in which the barrier properties were induced by glial cells. The effects of amyloid peptides have been tested on cell viability and barrier functions. A beta showed toxic effects on primary rat brain endothelial cells measured by MTT dye conversion and the lactate dehydrogenase release. Morphologically cytoplasmic vacuolization, disruption of the structure of cytoplasmic organelles and tight junctions could be observed in brain endothelial cells. Treatment with A beta(1-42) decreased the electrical resistance, and increased the permeability of brain endothelial cell monolayers for both fluorescein and albumin. Serum amyloid P component which stabilizes A beta fibrils in cortical amyloid plaques and cerebrovascular amyloid deposits significantly potentiated the barrier-weakening effect of A beta(1-42). Sulfated polysaccharide pentosan could decrease the toxic effects of A beta peptides in brain endothelial cells. It could also significantly protect the barrier integrity of monolayers from damaging actions of peptides. Pentosan modified the size, and significantly decreased the number of amyloid aggregates demonstrated by atomic force microscopy. The present data further support the toxic effects of amyloid peptides on brain endothelial cells, and can contribute to the development of molecules protecting the blood-brain barrier in Alzheimer's disease.