Modulation of inflammation in transgenic models of Alzheimer's disease.
Modulation of inflammation in transgenic models of Alzheimer's disease.
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DOI：
10.1186/1742-2094-11-25
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发表时间：
2014-02-03
影响因子：
9.3
通讯作者：
Sastre M
中科院分区：
文献类型：
--
作者：
Birch AM;Katsouri L;Sastre M
在过去的十年里，炎症过程一直是阿尔茨海默病(AD)领域日益关注的焦点，不仅因为它在神经元变性中的潜在作用，而且还因为它是一个有前途的治疗靶点。然而，最近在这一领域的研究提供了不同的结果，这主要是由于在进行调查时使用了不同的模型和疾病的不同阶段。现在公认的是，小胶质细胞，可能还有星形胶质细胞，在衰老和疾病阶段改变其激活表型，因此这些是确定不同炎症成分的功能以及潜在治疗方法的重要因素。使用阿尔茨海默病动物模型调节炎症提供了单独研究炎症成分和独立操纵淀粉样前体蛋白和tau转基因中的炎症基因的可能性。这也为这些因素可能影响AD病理的机制提供了一些线索。在这篇综述中，我们考察了不同的转基因方法和治疗方法，这些方法和治疗方法已被报道通过AD的动物模型来调节炎症。这些研究提供了证据表明，增强炎症与淀粉样β蛋白(Aβ)生成、Aβ聚集和tau磷酸化的增加有关。然而，tau磷酸化的改变可以独立于这些炎性介质对Aβ水平的改变。
Over the past decade the process of inflammation has been a focus of increasing interest in the Alzheimer’s disease (AD) field, not only for its potential role in neuronal degeneration but also as a promising therapeutic target. However, recent research in this field has provided divergent outcomes, largely due to the use of different models and different stages of the disease when the investigations have been carried out. It is now accepted that microglia, and possibly astrocytes, change their activation phenotype during ageing and the stage of the disease, and therefore these are important factors to have in mind to define the function of different inflammatory components as well as potential therapies. Modulating inflammation using animal models of AD has offered the possibility to investigate inflammatory components individually and manipulate inflammatory genes in amyloid precursor protein and tau transgenics independently. This has also offered some hints on the mechanisms by which these factors may affect AD pathology. In this review we examine the different transgenic approaches and treatments that have been reported to modulate inflammation using animal models of AD. These studies have provided evidence that enhancing inflammation is linked with increases in amyloid-beta (Aβ) generation, Aβ aggregation and tau phosphorylation. However, the alterations on tau phosphorylation can be independent of changes in Aβ levels by these inflammatory mediators.
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DOI：
10.1523/jneurosci.1729-12.2012
发表时间：
2012-10-24
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Cameron B;Tse W;Lamb R;Li X;Lamb BT;Landreth GE
通讯作者：
Landreth GE
影响因子：
16.2
作者：
Bhaskar, Kiran;Konerth, Megan;Kokiko-Cochran, Olga N.;Cardona, Astrid;Ransohoff, Richard M.;Lamb, Bruce T.
通讯作者：
Lamb, Bruce T.
影响因子：
15.1
作者：
Chen, Jing;Buchanan, Jessica B.;Johnson, Rodney W.
通讯作者：
Johnson, Rodney W.
影响因子：
4.2
作者：
Benzing, WC;Wujek, JR;Brunden, KR
通讯作者：
Brunden, KR
影响因子：
6.2
作者：
Familian, A;Boshuizen, RS;Veerhuis, R
通讯作者：
Veerhuis, R