Molecular Links Between Endothelial Dysfunction and Neurodegeneration in Alzheimer's Disease
Molecular Links Between Endothelial Dysfunction and Neurodegeneration in Alzheimer's Disease
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DOI：
10.2174/1567205010666131119235254
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发表时间：
2014-01-01
影响因子：
2.1
通讯作者：
Fassbender, Klaus
中科院分区：
文献类型：
--
作者：
Lyros, Epameinondas;Bakogiannis, Constantinos;Fassbender, Klaus
阿尔茨海默病 (AD) 的特点是认知功能进行性衰退，是最常见的痴呆症形式，也是现代西方社会发病和死亡的主要原因。越来越多的证据支持这样的假设：原发性脑血管功能障碍会引发一系列事件，导致阿尔茨海默氏痴呆症的神经元损伤。具体而言，内皮构成血脑屏障的一部分，其功能障碍被认为在疾病中淀粉样蛋白-β稳态紊乱和循环有毒分子浸润脑实质中发挥重要作用。此外，内皮本身在某些条件下能够产生神经毒性和炎症因子，而常见的生长因子则调节神经元和血管的发育和维持。内皮细胞和神经元细胞对线粒体完整性和细胞凋亡的常见分子途径的依赖也意味着血管病理学和神经变性之间存在联系。本文旨在回顾有关上述机制中涉及的分子参与者的现有证据，这些证据有可能开发生物标志物或新的治疗靶点。
Alzheimer's disease (AD) is characterized by a progressive decline of cognitive functions and represents the most common form of dementia and a major cause of morbidity and mortality in the modern, westernized societies. There is accumulating evidence to support the hypothesis that a primary cerebral vascular dysfunction initiates a cascade of events that lead to neuronal injury in Alzheimer's dementia. The endothelium, in specific, constitutes a part of the blood brain barrier, the dysfunction of which is thought to play an important role to disturbed amyloid-beta homeostasis and infiltration of the brain parenchyma with circulating toxic molecules in the disease. Furthermore, the endothelium itself is under certain conditions capable of producing neurotoxic and inflammatory factors, whereas common growth factors regulate the development and maintenance of both neurons and blood vessels. Reliance of both endothelial and neuronal cells on mitochondrial integrity and common molecular pathways for apoptosis also imply that there is a link between vascular pathology and neurodegeneration. The present article intends to review available evidence on molecular players implicated in the above mechanisms with the potential to develop biomarkers or novel therapeutic targets.