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阿尔茨海默病小鼠模型中趋化因子及其受体表达的变化。

Changes in Chemokines and Chemokine Receptors Expression in a Mouse Model of Alzheimer's Disease.

机构信息

Department of Physiology, School of Medicine, University of Valencia. Spain.

Faculty of Surgery and Chiropody, University of Valencia. Spain.

出版信息

Int J Biol Sci. 2019 Jan 1;15(2):453-463. doi: 10.7150/ijbs.26703. eCollection 2019.

Abstract

The amyloid precursor protein plus presenilin-1 (APP/PS1) mice are a frequently-used model for Alzheimer's disease studies (AD). However, the data relevant to which proteins are involved in inflammatory mechanism are not sufficiently well-studied using the AD mouse model. Using behavioral studies, quantitative RT-PCR and Western-blot techniques, significant findings were determined by the expression of proteins involved in inflammation comparing APP/PS1 and Wild type mice. Increased GFAP expression could be associated with the elevation in number of reactive astrocytes. IL-3 is involved in inflammation and ABDF1 intervenes normally in the transport across cell membranes and both were found up-regulated in APP/PS1 mice compared to Wild type mice. Furthermore, CCR5 expression was decreased and both CCL3 and CCL4 chemokines were highly expressed indicating a possible gliosis and probably an increase in chemotaxis from lymphocytes and T cell generation. We also noted for the first time, a CCR8 increase expression with diminution of its CCL1 chemokine, both normally involved in protection from bacterial infection and demyelination. Control of inflammatory proteins will be the next step in understanding the progression of AD and also in determining the mechanisms that can develop in this disease.

摘要

淀粉样前体蛋白加早老素-1(APP/PS1)小鼠是阿尔茨海默病研究(AD)中常用的模型。然而,使用 AD 小鼠模型对涉及炎症机制的哪些蛋白质进行的研究还不够充分。通过对 APP/PS1 和野生型小鼠进行比较,使用行为研究、定量 RT-PCR 和 Western blot 技术,确定了参与炎症的蛋白质表达的显著发现。GFAP 表达的增加可能与反应性星形胶质细胞数量的增加有关。IL-3 参与炎症,ABDF1 通常参与跨细胞膜的运输,与野生型小鼠相比,APP/PS1 小鼠中这两种物质的表达都上调。此外,CCR5 的表达减少,CCL3 和 CCL4 趋化因子的表达高度增加,表明可能发生神经胶质增生,可能导致淋巴细胞趋化性增加和 T 细胞生成增加。我们还首次注意到 CCR8 表达增加,其 CCL1 趋化因子减少,这两种物质通常都参与细菌感染和脱髓鞘的保护。控制炎症蛋白将是下一步理解 AD 进展的关键,也是确定这种疾病中可能发生的机制的关键。

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