Endothelial Dysfunction and Amyloid-β-Induced Neurovascular Alterations.
Endothelial Dysfunction and Amyloid-β-Induced Neurovascular Alterations.
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DOI：
10.1007/s10571-015-0256-9
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发表时间：
2016-03
影响因子：
4
通讯作者：
Park L
中科院分区：
文献类型：
--
作者：
Koizumi K;Wang G;Park L
阿尔茨海默病（Alzheimer 'sdisease，AD）和脑血管病有着共同的血管危险因素，对脑血管的调节有着灾难性的影响。内皮细胞，内衬脑血管的内壁，形成血液和脑之间的动态界面，并且对于维持神经血管稳态至关重要。因此，内皮细胞损伤被认为是血管调节机制受损的最早症状之一。β淀粉样蛋白（Aβ）的细胞外积聚是AD的主要致病因素。Aβ对脑血管具有潜在的有害作用，并损害内皮结构和功能。最近的证据表明血管氧化应激和内皮细胞上非选择性阳离子通道瞬时受体电位melastatin（TRPM）-2的激活在Aβ诱导的神经血管功能障碍的机制中。因此，Aβ触发内皮细胞中TRPM 2通道的开放，导致细胞内Ca 2+过载和血管功能障碍。脑血管功能障碍可能通过减少脑血供，增加血管功能不全的易感性，促进Aβ蓄积而参与AD的发病。最近认识到，血管因素有助于AD病理生物学提出了新的目标，预防和治疗这种毁灭性的疾病。
Alzheimer's disease (AD) and cerebrovascular diseases share common vascular risk factors that have disastrous effects on cerebrovascular regulation. Endothelial cells, lining inner walls of cerebral blood vessels, form a dynamic interface between the blood and the brain and are critical for the maintenance of neurovascular homeostasis. Accordingly, injury in endothelial cells is regarded as one of the earliest symptoms of impaired vasoregulatory mechanisms. Extracellular buildup of amyloid-β (Aβ) is a central pathogenic factor in AD. Aβ exerts potent detrimental effects on cerebral blood vessels and impairs endothelial structure and function. Recent evidence implicates vascular oxidative stress and activation of the nonselective cationic channel transient receptor potential melastatin (TRPM)-2 on endothelial cells in the mechanisms of Aβ-induced neurovascular dysfunction. Thus, Aβ triggers opening of TRPM2 channels in endothelial cells leading to intracellular Ca2+ overload and vasomotor dysfunction. The cerebrovascular dysfunction may contribute to AD pathogenesis by reducing the cerebral blood supply, leading to increased susceptibility to vascular insufficiency, and by promoting Aβ accumulation. The recent realization that vascular factors contribute to AD pathobiology suggests new targets for the prevention and treatment of this devastating disease.