Microglia and its Genetics in Alzheimer's Disease.
Microglia and its Genetics in Alzheimer's Disease.
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DOI：
10.2174/1567205018666211105140732
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发表时间：
2021
影响因子：
2.1
通讯作者：
Zhao, Zhen
中科院分区：
文献类型：
--
作者：
Liang, Xinyan;Wu, Haijian;Colt, Mark;Guo, Xinying;Pluimer, Brock;Zeng, Jianxiong;Dong, Shupeng;Zhao, Zhen
阿尔茨海默病（AD）是世界上最常见的痴呆症。虽然其发现和病理表现集中于淀粉样蛋白β（Aβ）和过度磷酸化的tau蛋白的蛋白聚集，但神经炎症在过去十年中已成为该疾病发病机制和进展的主要组成部分。小胶质细胞作为中枢神经系统（CNS）中主要的先天性免疫细胞类型，在调节神经炎症中发挥非常重要的作用，神经炎症在包括AD在内的神经退行性疾病中常见。在炎症反应下，小胶质细胞经历形态学变化和状态从稳态到活化形式的转变。在AD中已经鉴定出显示不同遗传特征的不同小胶质细胞亚型，并且这些特征通常与从全基因组关联研究（GWAS）中鉴定的AD风险基因（例如APOE和TREM2）相关联。此外，许多AD危险基因在小胶质细胞中高度富集，并特异性地影响小胶质细胞在发病机制中的功能，如释放炎性细胞因子和清除Aβ。因此，基于目前的临床前研究及其致病或保护作用，在小胶质细胞中建立这些风险基因的景观，将在很大程度上帮助我们了解AD的复杂病因学，并为有效治疗的未满足需求提供新的见解。
Alzheimer’s Disease (AD) is the most prevalent form of dementia across the world. While its discovery and pathological manifestations are centered on protein aggregations of amyloid-beta (Aβ) and hyperphosphorylated tau protein, neuroinflammation has emerged in the last decade as a main component of the disease in both pathogenesis and progression. As the main innate immune cell type in central nervous system (CNS), microglia play a very important role in regulating neuroinflammation, which occurs commonly in neurodegenerative conditions including AD. Under inflammatory response, microglia undergo morphological changes and status transition from homeostatic to activated forms. Different microglia subtypes displaying distinct genetic profiles have been identified in AD, and these signatures often link to AD risk genes identified from the genome-wide association studies (GWAS), such as APOE and TREM2. Furthermore, many of AD risk genes are highly enriched in microglia and specifically influence the functions of microglia in pathogenesis, e.g. releasing inflammatory cytokines and clearing Aβ. Therefore, building up a landscape of these risk genes in microglia, based on current preclinical studies and in the context of their pathogenic or protective effects, would largely help us to understand the complexed etiology of AD and provide new insight for the unmet need of effective treatment.
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影响因子：
9.3
作者：
Cherry JD;Olschowka JA;O'Banion MK
通讯作者：
O'Banion MK
影响因子：
12.3
作者：
Antúnez C;Boada M;González-Pérez A;Gayán J;Ramírez-Lorca R;Marín J;Hernández I;Moreno-Rey C;Morón FJ;López-Arrieta J;Mauleón A;Rosende-Roca M;Noguera-Perea F;Legaz-García A;Vivancos-Moreau L;Velasco J;Carrasco JM;Alegret M;Antequera-Torres M;Manzanares S;Romo A;Blanca I;Ruiz S;Espinosa A;Castaño S;García B;Martínez-Herrada B;Vinyes G;Lafuente A;Becker JT;Galán JJ;Serrano-Ríos M;Alzheimer's Disease Neuroimaging Initiative;Vázquez E;Tárraga L;Sáez ME;López OL;Real LM;Ruiz A
通讯作者：
Ruiz A
DOI：
10.1523/jneurosci.1729-12.2012
发表时间：
2012-10-24
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Cameron B;Tse W;Lamb R;Li X;Lamb BT;Landreth GE
通讯作者：
Landreth GE
影响因子：
14
作者：
通讯作者：
--
DOI：
10.1073/pnas.0812697106
发表时间：
2009-02-10
影响因子：
11.1
作者：
Agosta, Federica;Vossel, Keith A.;Gorno-Tempini, Maria Luisa
通讯作者：
Gorno-Tempini, Maria Luisa