阿尔茨海默病的神经炎症:小胶质细胞特征及其与疾病的相关性。

IF 5 3区 医学 Q2 IMMUNOLOGY
Akira Sobue, Okiru Komine, Koji Yamanaka
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引用次数: 7

摘要

阿尔茨海默病(AD)是最常见的痴呆形式,病理特征为老年斑和神经原纤维缠结(nft),导致神经退行性变。神经炎症,定义为神经胶质细胞如小胶质细胞和星形胶质细胞的激活,在AD患者的老年斑和受影响的神经元周围观察到。最近进行的全基因组关联研究(GWAS)表明,大部分已确定的阿尔茨海默病风险基因参与免疫反应,并在小胶质细胞中富集。小胶质细胞是中枢神经系统(CNS)的先天免疫细胞,参与免疫监视和维持中枢神经系统的内稳态。最近,在AD模型小鼠中发现了一种新的活化小胶质细胞亚群,称为疾病相关小胶质细胞(DAM),也称为活化反应小胶质细胞(ARM)或小胶质神经退行性表型(MGnD)。这些小胶质细胞与β-淀粉样蛋白(Aβ)斑块密切相关,并表现出特有的基因表达谱,同时伴有稳态小胶质基因的表达减少。然而,尚不清楚内稳态小胶质细胞功能的下降或DAM/ARM/MGnD功能的增加是否与阿尔茨海默病中神经元损失的程度相关。为了将啮齿动物的研究结果转化为人类阿尔茨海默病,临床前阿尔茨海默病中易受β-淀粉样蛋白积累的大脑区域楔前叶引起了人们的高度关注,因为它可以为早期阿尔茨海默病中小胶质细胞对Aβ的反应机制提供新的见解。在本研究中,我们比较分析了三种具有代表性的神经退行性小鼠模型和早期AD病理的人类precei的小胶质细胞基因表达谱。我们继续评估已鉴定的基因作为AD的潜在治疗靶点。我们相信我们的发现将为更好地理解神经胶质功能障碍在阿尔茨海默病中的作用提供重要的资源。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Neuroinflammation in Alzheimer's disease: microglial signature and their relevance to disease.

Neuroinflammation in Alzheimer's disease: microglial signature and their relevance to disease.

Alzheimer's disease (AD) is the most common form of dementia, pathologically characterized by senile plaques and neurofibrillary tangles (NFTs), resulting in neurodegeneration. Neuroinflammation, defined as the activation of glial cells such as microglia and astrocytes, is observed surrounding senile plaques and affected neurons in AD. Recently conducted genome-wide association studies (GWAS) indicate that a large section of identified AD risk genes are involved in immune responses and are enriched in microglia. Microglia are innate immune cells in the central nervous system (CNS), which are involved in immune surveillance and maintenance of homeostasis in the CNS. Recently, a novel subpopulation of activated microglia named as disease-associated microglia (DAM), also known as activated response microglia (ARM) or microglial neurodegenerative phenotype (MGnD), was identified in AD model mice. These microglia closely associate with β-amyloid (Aβ) plaques and exhibit characteristic gene expression profiles accompanied with reduced expressions of homeostatic microglial genes. However, it remains unclear whether decreased homeostatic microglia functions or increased DAM/ARM/MGnD functions correlate with the degree of neuronal loss in AD. To translate the results of rodent studies to human AD, precuneus, the brain region vulnerable to β-amyloid accumulation in preclinical AD, is of high interest, as it can provide novel insights into the mechanisms of microglia response to Aβ in early AD. In this study, we performed comparative analyses of gene expression profiles of microglia among three representative neurodegenerative mouse models and the human precunei with early AD pathology. We proceeded to evaluate the identified genes as potential therapeutic targets for AD. We believe that our findings will provide important resources to better understand the role of glial dysfunction in AD.

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来源期刊
CiteScore
11.10
自引率
1.20%
发文量
45
审稿时长
11 weeks
期刊介绍: Inflammation and Regeneration is the official journal of the Japanese Society of Inflammation and Regeneration (JSIR). This journal provides an open access forum which covers a wide range of scientific topics in the basic and clinical researches on inflammation and regenerative medicine. It also covers investigations of infectious diseases, including COVID-19 and other emerging infectious diseases, which involve the inflammatory responses. Inflammation and Regeneration publishes papers in the following categories: research article, note, rapid communication, case report, review and clinical drug evaluation.
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