摘要
阿尔茨海默病(AD)是世界上最常见的痴呆症。尽管它的发现和病理表现集中于淀粉样蛋白- β (a β)和tau蛋白的过度磷酸化,但在过去的十年中,神经炎症已经成为该疾病的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)中主要的先天免疫细胞类型,在调节神经炎症中发挥着非常重要的作用,神经炎症常见于神经退行性疾病,包括AD。在炎症反应下,小胶质细胞发生形态变化,从稳态状态转变为激活状态。在AD中,不同的小胶质细胞亚型表现出不同的遗传特征,这些特征通常与从全基因组关联研究(GWAS)中识别出的AD风险基因有关,如APOE和TREM2。此外,许多AD风险基因在小胶质细胞中高度富集,并特异性影响小胶质细胞在发病过程中的功能,如释放炎症细胞因子和清除Aβ。因此,基于目前的临床前研究以及它们的致病或保护作用,建立小胶质细胞中这些风险基因的景观,将在很大程度上帮助我们理解AD复杂的病因,并为有效治疗的未满足的需求提供新的见解。
关键词: 阿尔茨海默病,小胶质细胞,神经炎症,AD风险基因,APOE, GWAS。
Current Alzheimer Research
Title:Microglia and its Genetics in Alzheimer's Disease
Volume: 18 Issue: 9
关键词: 阿尔茨海默病,小胶质细胞,神经炎症,AD风险基因,APOE, GWAS。
摘要: 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 terms of both pathogenesis and progression. As the main innate immune cell type in the 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 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 complex etiology of AD and provide new insight into the unmet need for effective treatment.
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Cite this article as:
Microglia and its Genetics in Alzheimer's Disease, Current Alzheimer Research 2021; 18 (9) . https://dx.doi.org/10.2174/1567205018666211105140732
DOI https://dx.doi.org/10.2174/1567205018666211105140732 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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