Deciphering the Astrocyte Reaction in Alzheimer's Disease.
Deciphering the Astrocyte Reaction in Alzheimer's Disease.
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DOI：
10.3389/fnagi.2018.00114
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发表时间：
2018
影响因子：
4.8
通讯作者：
Serrano-Pozo A
中科院分区：
文献类型：
--
作者：
Perez-Nievas BG;Serrano-Pozo A
几十年前，反应性星形胶质细胞被鉴定为阿尔茨海默病(AD)患者大脑皮质中老年淀粉样斑块的一种成分。然而，自那以后，它们在AD病理生理学中的作用一直难以捉摸，部分原因是文献从原代星形胶质细胞培养和急性脑损伤模型外推到慢性神经退行性变的情景。最近越来越多的证据支持这一观点，即AD中反应性星形胶质细胞具有神经毒性特性，可能是由于毒性功能的获得和神经营养作用的丧失。然而，这种胶质细胞的多样性和复杂性才刚刚开始揭开面纱，预计星形胶质细胞的反应也可能是异质性的。在这里，我们回顾了AD小鼠模型和人类神经病理学研究的证据，并试图破解星形胶质细胞对我们理解AD的发展和进展构成的主要难题。我们讨论了AD脑内星形胶质细胞反应的形态特征，星形胶质细胞反应对星形胶质细胞生物学和AD病理特征的影响，以及参与这一反应的分子途径。
Reactive astrocytes were identified as a component of senile amyloid plaques in the cortex of Alzheimer’s disease (AD) patients several decades ago. However, their role in AD pathophysiology has remained elusive ever since, in part owing to the extrapolation of the literature from primary astrocyte cultures and acute brain injury models to a chronic neurodegenerative scenario. Recent accumulating evidence supports the idea that reactive astrocytes in AD acquire neurotoxic properties, likely due to both a gain of toxic function and a loss of their neurotrophic effects. However, the diversity and complexity of this glial cell is only beginning to be unveiled, anticipating that astrocyte reaction might be heterogeneous as well. Herein we review the evidence from mouse models of AD and human neuropathological studies and attempt to decipher the main conundrums that astrocytes pose to our understanding of AD development and progression. We discuss the morphological features that characterize astrocyte reaction in the AD brain, the consequences of astrocyte reaction for both astrocyte biology and AD pathological hallmarks, and the molecular pathways that have been implicated in this reaction.
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影响因子：
12.7
作者：
Arbel-Ornath M;Hudry E;Eikermann-Haerter K;Hou S;Gregory JL;Zhao L;Betensky RA;Frosch MP;Greenberg SM;Bacskai BJ
通讯作者：
Bacskai BJ
DOI：
10.1523/jneurosci.1064-09.2009
发表时间：
2009-10-14
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Abdul HM;Sama MA;Furman JL;Mathis DM;Beckett TL;Weidner AM;Patel ES;Baig I;Murphy MP;LeVine H 3rd;Kraner SD;Norris CM
通讯作者：
Norris CM
影响因子：
2.5
作者：
Akiyama, H;Schwab, C;McGeer, PL
通讯作者：
McGeer, PL
DOI：
10.1016/s0169-328x(98)00066-7
发表时间：
1998-06-01
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Bales, KR;Du, YS;Paul, SM
通讯作者：
Paul, SM
DOI：
10.1073/pnas.1206171109
发表时间：
2012-05-29
影响因子：
11.1
作者：
Busche, Marc Aurel;Chen, Xiaowei;Konnerth, Arthur
通讯作者：
Konnerth, Arthur