文献检索文档翻译深度研究
Suppr Zotero 插件Zotero 插件
邀请有礼套餐&价格历史记录

新学期,新优惠

限时优惠:9月1日-9月22日

30天高级会员仅需29元

1天体验卡首发特惠仅需5.99元

了解详情
不再提醒
插件&应用
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
高级版
套餐订阅购买积分包
AI 工具
文献检索文档翻译深度研究
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利:CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2025

人类神经退行性疾病中小胶质细胞的免疫表型:检测人类大脑中小胶质细胞极化的挑战

Immune phenotypes of microglia in human neurodegenerative disease: challenges to detecting microglial polarization in human brains.

作者信息

Walker Douglas G, Lue Lih-Fen

机构信息

Laboratory of Neuroinflammation, Banner Sun Health Research Institute, 10515 West Santa Fe Drive, Sun City, AZ, 85351, USA.

出版信息

Alzheimers Res Ther. 2015 Aug 19;7(1):56. doi: 10.1186/s13195-015-0139-9.


DOI:10.1186/s13195-015-0139-9
PMID:26286145
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4543480/
Abstract

Inflammatory responses in the brain, which can be demonstrated by changes in properties of microglia, the brain-resident macrophages, are a common feature of human neurodegenerative diseases. Different monocyte/macrophage phenotypes have been defined by changes in expression of cytokines, receptors and other markers as a response to different classes of stimuli. Monocytes, macrophages and microglia can have a range of phenotypes with associated properties depending on their microenvironment. Macrophage/microglia polarization states have been defined as classical activation (M1), alternative activation (M2a), type II alternative activation (M2b) or acquired deactivation (M2c). Available markers for identifying microglial phenotypes in human brains are still limited; those available provide incomplete information on the functions or polarization states of microglia observed in tissues from diseases such as Alzheimer's disease, Parkinson's disease and multiple sclerosis. The most widely used marker to describe activated microglia in human brains, particularly diseased brains, has been HLA-DR, the major histocompatibility complex II protein. HLA-DR-positive microglia can have a wide range of activation morphologies that are affected not only by disease pathology, but also by their differentiation states and brain regions. Two other widely used markers to identify microglia in human brains are ionized calcium binding adaptor molecule-1 and CD68. Although their expression changes in diseased brains, these markers do not show specificity for different phenotypes. Over the years there have been studies with additional markers that attempt to further define microglial properties, particularly in Alzheimer's disease brains. Most studies have employed immunohistochemical techniques to identify microglia in tissue sections, but recent advances in this field have allowed gene expression profiling of microglia upon immediate isolation from brains. We will review which markers might better define different activation phenotypes of microglia in human brains and whether they fit into current microglial polarization schemes.

摘要

大脑中的炎症反应是人类神经退行性疾病的一个常见特征,这可以通过脑内常驻巨噬细胞——小胶质细胞的特性变化来证明。不同的单核细胞/巨噬细胞表型是由细胞因子、受体和其他标志物表达的变化所定义的,这些变化是对不同类型刺激的反应。单核细胞、巨噬细胞和小胶质细胞可以具有一系列取决于其微环境的表型及相关特性。巨噬细胞/小胶质细胞的极化状态已被定义为经典激活(M1)、替代激活(M2a)、II型替代激活(M2b)或获得性失活(M2c)。用于识别人类大脑中小胶质细胞表型的现有标志物仍然有限;现有的标志物提供的关于在阿尔茨海默病、帕金森病和多发性硬化症等疾病组织中观察到的小胶质细胞功能或极化状态的信息并不完整。在人类大脑中,尤其是患病大脑中,描述活化小胶质细胞最广泛使用的标志物是主要组织相容性复合体II类蛋白HLA-DR。HLA-DR阳性小胶质细胞可以具有广泛的激活形态,这些形态不仅受疾病病理学影响,还受其分化状态和脑区的影响。另外两个广泛用于识别人类大脑中小胶质细胞的标志物是离子钙结合衔接分子1和CD68。尽管它们在患病大脑中的表达会发生变化,但这些标志物并未显示出对不同表型的特异性。多年来,有一些研究使用了其他标志物,试图进一步定义小胶质细胞的特性,特别是在阿尔茨海默病大脑中。大多数研究采用免疫组织化学技术在组织切片中识别小胶质细胞,但该领域的最新进展使得能够在从小脑立即分离后对小胶质细胞进行基因表达谱分析。我们将综述哪些标志物可能更好地定义人类大脑中小胶质细胞的不同激活表型,以及它们是否符合当前的小胶质细胞极化模式。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ed2/4543480/b6736a4af773/13195_2015_139_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ed2/4543480/baee45acbd77/13195_2015_139_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ed2/4543480/b6736a4af773/13195_2015_139_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ed2/4543480/baee45acbd77/13195_2015_139_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ed2/4543480/b6736a4af773/13195_2015_139_Fig2_HTML.jpg

相似文献

[1]
Immune phenotypes of microglia in human neurodegenerative disease: challenges to detecting microglial polarization in human brains.

Alzheimers Res Ther. 2015-8-19

[2]
Patterns of Expression of Purinergic Receptor P2RY12, a Putative Marker for Non-Activated Microglia, in Aged and Alzheimer's Disease Brains.

Int J Mol Sci. 2020-1-20

[3]
TMEM119 marks a subset of microglia in the human brain.

Neuropathology. 2016-2

[4]
Exploring the Significance of Microglial Phenotypes and Morphological Diversity in Neuroinflammation and Neurodegenerative Diseases: From Mechanisms to Potential Therapeutic Targets.

Immunol Invest. 2024-8

[5]
Microglial Phenotyping in Neurodegenerative Disease Brains: Identification of Reactive Microglia with an Antibody to Variant of CD105/Endoglin.

Cells. 2019-7-23

[6]
Expression of immunohistochemical markers on microglia in Creutzfeldt-Jakob disease and Alzheimer's disease: morphometric study and review of the literature.

Folia Neuropathol. 2012

[7]
Staining of HLA-DR, Iba1 and CD68 in human microglia reveals partially overlapping expression depending on cellular morphology and pathology.

J Neuroimmunol. 2017-8-15

[8]
Down syndrome individuals with Alzheimer's disease have a distinct neuroinflammatory phenotype compared to sporadic Alzheimer's disease.

Neurobiol Aging. 2015-9

[9]
Differential Roles of M1 and M2 Microglia in Neurodegenerative Diseases.

Mol Neurobiol. 2016-3

[10]
Beyond Activation: Characterizing Microglial Functional Phenotypes.

Cells. 2021-8-28

引用本文的文献

[1]
MS4A6A/Ms4a6d deficiency disrupts neuroprotective microglia functions and promotes inflammation in Alzheimer's disease model.

Mol Neurodegener. 2025-8-28

[2]
Ginsenoside Rb1 attenuates neuroflammation via activating Wnt/β-catenin signaling pathway to exert neuroprotective effect on cerebral ischemic-reperfusion injury.

Front Aging Neurosci. 2025-8-6

[3]
Macrophages: Subtypes, Distribution, Polarization, Immunomodulatory Functions, and Therapeutics.

MedComm (2020). 2025-7-25

[4]
Depression exacerbates AD pathology through lactate-dependent activation of microglial Kv1.3 to promote Aβ-containing exosome spreading.

J Neuroinflammation. 2025-6-27

[5]
Prenatal opioid exposure and maternal HCV infection impair microglia development and function: A patient-specific in vitro model.

Brain Behav Immun. 2025-6-9

[6]
Neuroinflammation associated with proviral DNA persists in the brain of virally suppressed people with HIV.

Front Immunol. 2025-5-21

[7]
NMDA receptor antagonists mitigate COVID-19-induced neuroinflammation and improve survival in a mouse model.

Sci Rep. 2025-6-4

[8]
Loss of insulin signaling in microglia impairs cellular uptake of Aβ and neuroinflammatory response exacerbating AD-like neuropathology.

Proc Natl Acad Sci U S A. 2025-5-27

[9]
p16-expressing microglia and endothelial cells promote tauopathy and neurovascular abnormalities in PS19 mice.

Neuron. 2025-7-23

[10]
TAMing Gliomas: Unraveling the Roles of Iba1 and CD163 in Glioblastoma.

Cancers (Basel). 2025-4-26

本文引用的文献

[1]
Neuroinflammation in Alzheimer's disease.

Lancet Neurol. 2015-4

[2]
Activation status of human microglia is dependent on lesion formation stage and remyelination in multiple sclerosis.

J Neuropathol Exp Neurol. 2015-1

[3]
Association of CD33 polymorphism rs3865444 with Alzheimer's disease pathology and CD33 expression in human cerebral cortex.

Neurobiol Aging. 2015-2

[4]
TREM2 Protein Expression Changes Correlate with Alzheimer's Disease Neurodegenerative Pathologies in Post-Mortem Temporal Cortices.

Brain Pathol. 2015-7

[5]
Microglial phenotypes and toll-like receptor 2 in the substantia nigra and hippocampus of incidental Lewy body disease cases and Parkinson's disease patients.

Acta Neuropathol Commun. 2014-8-7

[6]
CSF1 overexpression has pleiotropic effects on microglia in vivo.

Glia. 2014-12

[7]
Microglial dynamics and role in the healthy and diseased brain: a paradigm of functional plasticity.

Neuroscientist. 2015-4

[8]
The M1 and M2 paradigm of macrophage activation: time for reassessment.

F1000Prime Rep. 2014-3-3

[9]
Phenotypic profile of alternative activation marker CD163 is different in Alzheimer's and Parkinson's disease.

Acta Neuropathol Commun. 2014-2-14

[10]
Neuroinflammatory phenotypes and their roles in Alzheimer's disease.

Neurodegener Dis. 2013-9-6

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

推荐工具

医学文档翻译智能文献检索