The pericyte: a forgotten cell type with important implications for Alzheimer's disease?
The pericyte: a forgotten cell type with important implications for Alzheimer's disease?
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DOI：
10.1111/bpa.12152
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发表时间：
2014-07
期刊：
影响因子：
--
通讯作者：
Zlokovic BV
中科院分区：
文献类型：
--
作者：
Winkler EA;Sagare AP;Zlokovic BV
周细胞是血脑屏障中的细胞，在阿尔茨海默病(AD)中退化，阿尔茨海默病(AD)是一种神经退行性疾病，其特征是早期神经血管功能障碍、淀粉样蛋白β肽(Aβ)升高、tau病理和神经元丢失导致进行性认知能力下降和痴呆。周细胞位于脑毛细血管内皮细胞、星形胶质细胞和神经元之间的神经血管单位内。最近的研究表明，周细胞调节关键的神经血管功能，包括血脑屏障的形成和维持，血管的稳定性和血管构筑，毛细血管血流的调节，以及中枢神经系统(CNS)正常功能所必需的有毒细胞副产物的清除。在这里，我们回顾了神经血管单位的概念和中枢神经系统周细胞的神经血管功能。接下来，我们讨论血管在AD中的作用，并综述周细胞在AD发病机制中的新作用，如血管介导的Aβ非依赖性神经退行性变，调节Aβ清除，以及在tau病理、神经元丢失和认知功能下降中的作用。我们的结论是，未来的研究应集中在周细胞与神经血管单位内的邻近细胞，即内皮细胞、星形胶质细胞和神经元之间异常信号转导的分子机制和途径，这可能是控制AD周细胞变性和继发性血管和神经元变性的潜在治疗靶点。
Pericytes are cells in the blood-brain barrier (BBB) that degenerate in Alzheimer’s disease (AD), a neurodegenerative disorder characterized by early neurovascular dysfunction, elevation of amyloid β-peptide (Aβ), tau pathology and neuronal loss leading to progressive cognitive decline and dementia. Pericytes are uniquely positioned within the neurovascular unit between endothelial cells of brain capillaries, astrocytes and neurons. Recent studies have shown that pericytes regulate key neurovascular functions including BBB formation and maintenance, vascular stability and angioarchitecture, regulation of capillary blood flow, and clearance of toxic cellular byproducts necessary for normal functioning of the central nervous system (CNS). Here, we review the concept of the neurovascular unit and neurovascular functions of CNS pericytes. Next, we discuss vascular contributions to AD, and review new roles of pericytes in the pathogenesis of AD such as vascular-mediated Aβ-independent neurodegeneration, regulation of Aβ clearance, and contributions to tau pathology, neuronal loss and cognitive decline. We conclude that future studies should focus on molecular mechanisms and pathways underlying aberrant signal transduction between pericytes and its neighboring cells within the neurovascular unit, i.e., endothelial cells, astrocytes and neurons, that could represent potential therapeutic targets to control pericyte degeneration in AD and the resulting secondary vascular and neuronal degeneration.
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DOI：
10.1073/pnas.0608251104
发表时间：
2007-01-16
影响因子：
11.1
作者：
Chow, Nienwen;Bell, Robert D.;Zlokovic, Berislav V.
通讯作者：
Zlokovic, Berislav V.
影响因子：
21.3
作者：
Bell, Robert D.;Deane, Rashid;Chow, Nienwen;Long, Xiaochun;Sagare, Abhay;Singh, Itender;Streb, Jeffrey W.;Guo, Huang;Rubio, Anna;Van Nostrand, William;Miano, Joseph M.;Zlokovic, Berislav V.
通讯作者：
Zlokovic, Berislav V.
DOI：
10.3233/jad-2011-0010
发表时间：
2011
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
作者：
Austin BP;Nair VA;Meier TB;Xu G;Rowley HA;Carlsson CM;Johnson SC;Prabhakaran V
通讯作者：
Prabhakaran V
影响因子：
3.7
作者：
Allinson KR;Lee HS;Fruttiger M;McCarty JH;Arthur HM
通讯作者：
Arthur HM
影响因子：
64.8
作者：
Armulik, Annika;Genove, Guillem;Betsholtz, Christer
通讯作者：
Betsholtz, Christer