APOE聚集在小胶质细胞，阿尔茨海默病的种子b-淀粉样变。

IF 3.6 3区医学 Q3 CELL BIOLOGY

Journal of Leukocyte Biology Pub Date : 2025-04-23 DOI:10.1093/jleuko/qiaf007

Miguel A Jiménez-Acosta, Cristina A Luckie-Duque, Marco A Meraz-Ríos

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引用次数: 0

摘要

有害蛋白聚集体的种子性增殖是阿尔茨海默病（AD）病理生理学的基础，尽管这种病理级联的开始仍未完全阐明。Kaji等人开发了一种表达halotag标记APOE的转基因敲入小鼠，并在表现淀粉样蛋白-β (a β)淀粉样变性的动物中发现了APOE的纤维聚集体。β-片结合染料检测阳性的APOE聚集体诱导小胶质细胞内溶酶体系统发生a β淀粉样变性，这一过程受小胶质细胞脂质代谢和JAK/STAT信号通路调节，表明小胶质细胞内吞吸收和聚集APOE可启动a β-斑块形成。

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Apolipoprotein E aggregation in microglia, seeds β-amyloidosis in Alzheimer's disease.

The seeded proliferation of harmful protein aggregates is fundamental to the pathophysiology of Alzheimer's disease (AD), although the initiation of this pathological cascade remains incompletely elucidated. Kaji et al. have developed a transgenic knockin mouse that expresses HaloTag-tagged APOE and discovered fibrillary aggregates of APOE in animals exhibiting amyloid-β (Aβ) amyloidosis. The APOE aggregates that tested positive for β-sheet-binding dyes induced Aβ amyloidosis in the endo-lysosomal system of microglia, a process modulated by microglial lipid metabolism and the JAK/STAT signaling pathway, indicating that the endocytic uptake and aggregation of APOE by microglia can initiate Aβ-plaque formation.

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来源期刊

Journal of Leukocyte Biology 医学-免疫学

CiteScore

11.50

自引率

0.00%

发文量

358

审稿时长

2 months

期刊介绍： JLB is a peer-reviewed, academic journal published by the Society for Leukocyte Biology for its members and the community of immunobiologists. The journal publishes papers devoted to the exploration of the cellular and molecular biology of granulocytes, mononuclear phagocytes, lymphocytes, NK cells, and other cells involved in host physiology and defense/resistance against disease. Since all cells in the body can directly or indirectly contribute to the maintenance of the integrity of the organism and restoration of homeostasis through repair, JLB also considers articles involving epithelial, endothelial, fibroblastic, neural, and other somatic cell types participating in host defense. Studies covering pathophysiology, cell development, differentiation and trafficking; fundamental, translational and clinical immunology, inflammation, extracellular mediators and effector molecules; receptors, signal transduction and genes are considered relevant. Research articles and reviews that provide a novel understanding in any of these fields are given priority as well as technical advances related to leukocyte research methods.