Tau Protein and Its Role in Blood-Brain Barrier Dysfunction.
Tau Protein and Its Role in Blood-Brain Barrier Dysfunction.
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DOI：
10.3389/fnmol.2020.570045
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发表时间：
2020
影响因子：
4.8
通讯作者：
Kovac A
中科院分区：
文献类型：
--
作者：
Michalicova A;Majerova P;Kovac A
血脑屏障（BBB）在维持中枢神经系统（CNS）的特殊微环境中发挥着至关重要的作用。随着年龄的增长，血脑屏障的稳定性下降，渗透性增加。涉及血脑屏障功能障碍的中枢神经系统疾病列表正在不断增加。血脑屏障的开放和随后的血清成分向大脑的渗透可导致一系列过程，导致进行性突触、神经元功能障碍和有害的神经炎症变化。这些过程与不同的疾病有关，包括血管性痴呆、中风、阿尔茨海默病（AD）、帕金森病、多发性硬化症、肌萎缩侧索硬化症、缺氧、缺血和糖尿病。在缺乏β-淀粉样蛋白过量产生的tau蛋白病中也观察到了BBB损伤，这表明tau蛋白在BBB损伤中发挥着作用。 Tau蛋白病代表大约 20 种不同的神经退行性疾病，其特征是神经系统细胞中 MAPT 的异常沉积。 tau 病的神经病理学定义为神经原纤维缠结 (NFT) 的细胞内积聚，由 tau 蛋白聚集的过度磷酸化和异常磷酸化以及神经炎症组成。 tau蛋白病中发现的血脑屏障破坏是由慢性神经炎症引起的。神经胶质细胞、神经元和内皮细胞产生促炎信号分子，如细胞因子、趋化因子和粘附分子，决定了血脑屏障的完整性和免疫细胞向大脑的迁移。炎症过程促进毛细血管的结构变化，例如周细胞破碎、增厚、萎缩、基底膜中层粘连蛋白的积累以及血管对血浆蛋白的通透性增加。在此，我们总结了有关tau蛋白在BBB结构和功能变化中的作用的知识。
The blood–brain barrier (BBB) plays a crucial role in maintaining the specialized microenvironment of the central nervous system (CNS). In aging, the stability of the BBB declines and the permeability increases. The list of CNS pathologies involving BBB dysfunction is growing. The opening of the BBB and subsequent infiltration of serum components to the brain can lead to a host of processes resulting in progressive synaptic, neuronal dysfunction, and detrimental neuroinflammatory changes. Such processes have been implicated in different diseases, including vascular dementia, stroke, Alzheimer’s disease (AD), Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis, hypoxia, ischemia, and diabetes mellitus. The BBB damage is also observed in tauopathies that lack amyloid-β overproduction, suggesting a role for tau in BBB damage. Tauopathies represent a heterogeneous group of around 20 different neurodegenerative diseases characterized by abnormal deposition of the MAPT in cells of the nervous system. Neuropathology of tauopathies is defined as intracellular accumulation of neurofibrillary tangles (NFTs) consisting of aggregated hyper- and abnormal phosphorylation of tau protein and neuroinflammation. Disruption of the BBB found in tauopathies is driven by chronic neuroinflammation. Production of pro-inflammatory signaling molecules such as cytokines, chemokines, and adhesion molecules by glial cells, neurons, and endothelial cells determine the integrity of the BBB and migration of immune cells into the brain. The inflammatory processes promote structural changes in capillaries such as fragmentation, thickening, atrophy of pericytes, accumulation of laminin in the basement membrane, and increased permeability of blood vessels to plasma proteins. Here, we summarize the knowledge about the role of tau protein in BBB structural and functional changes.
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影响因子：
12.7
作者：
Ahmed, Zeshan;Bigio, Eileen H.;Kovacs, Gabor G.
通讯作者：
Kovacs, Gabor G.
影响因子：
3.3
作者：
Askarova, S.;Yang, X.;Sheng, W.;Sun, G. Y.;Lee, J. C-M
通讯作者：
Lee, J. C-M
影响因子：
1.6
作者：
Chiaravalloti, Agostino;Fiorentini, Alessandro;Schillaci, Orazio
通讯作者：
Schillaci, Orazio
影响因子：
2.1
作者：
Deane, Rashid;Zlokovic, Berislav V.
通讯作者：
Zlokovic, Berislav V.
影响因子：
3.3
作者：
Bartels, A. L.;Willemsen, A. T. M.;Kortekaas, R.;de Jong, B. M.;de Vries, R.;de Klerk, O.;van Oostrom, J. C. H.;Portman, A.;Leenders, K. L.
通讯作者：
Leenders, K. L.