Transgenic mouse models of Alzheimer's disease.
Transgenic mouse models of Alzheimer's disease.
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DOI：
10.1002/msj.20159
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发表时间：
2010-01
影响因子：
--
通讯作者：
De Gasperi, Rita
中科院分区：
文献类型：
--
作者：
Elder, Gregory A.;Sosa, Miguel A. Gama;De Gasperi, Rita
阿尔茨海默病是美国和欧洲老年痴呆症最常见的原因。目前尚无有效的治疗方法。鉴于该病的流行和预后不良，动物模型的开发一直是研究的重点。转基因建模一直在淀粉样蛋白假说的基础上进行，并利用了淀粉样蛋白前体蛋白和早老素的突变，导致家族性阿尔茨海默病。在小鼠中建模一直是最积极的追求，因为基因修饰技术已经很发达。现在存在的转基因小鼠模型模拟了一系列阿尔茨海默病相关的病理。虽然没有一个模型完全复制人类疾病，但这些模型对β-淀粉样蛋白毒性的病理生理学，特别是关于不同β-淀粉样蛋白种类的影响和β-淀粉样蛋白寡聚体的可能致病作用，提供了重要的见解。它们还被广泛用于潜在治疗方式的临床前测试，并在目前处于临床试验中的阿尔茨海默病免疫疗法的开发中发挥了关键作用。毫无疑问，这些模型将继续在临床前测试中发挥核心作用，并被用作深入了解阿尔茨海默病生物学基础的工具。
Alzheimer’s disease is the most common cause of senile dementia in the United States and Europe. At present, there is no effective treatment. Given the disease’s prevalence and poor prognosis, the development of animal models has been a high research priority. Transgenic modeling has been pursued on the basis of the amyloid hypothesis and has taken advantage of mutations in the amyloid precursor protein and the presenilins that cause familial forms of Alzheimer’s disease. Modeling has been most aggressively pursued in mice, for which the techniques of genetic modification are well developed. Transgenic mouse models now exist that mimic a range of Alzheimer’s disease–related pathologies. Although none of the models fully replicates the human disease, the models have contributed significant insights into the pathophysiology of β-amyloid toxicity, particularly with respect to the effects of different β-amyloid species and the possible pathogenic role of β-amyloid oligomers. They have also been widely used in the preclinical testing of potential therapeutic modalities and have played a pivotal role in the development of immunotherapies for Alzheimer’s disease that are currently in clinical trials. These models will, without a doubt, continue to play central roles in preclinical testing and be used as tools for developing insights into the biological basis of Alzheimer’s disease.
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影响因子：
82.9
作者：
Citron, M;Westaway, D;Selkoe, DJ
通讯作者：
Selkoe, DJ
影响因子：
5.3
作者：
Adlard, PA;Perreau, VM;Cotman, CW
通讯作者：
Cotman, CW
影响因子：
64.8
作者：
Chen, GQ;Chen, KS;Morris, RGM
通讯作者：
Morris, RGM
影响因子：
6.1
作者：
Dodart, JC;Mathis, C;Ungerer, A
通讯作者：
Ungerer, A
DOI：
10.1073/pnas.151261398
发表时间：
2001-07-17
影响因子：
11.1
作者：
DeMattos, RB;Bales, KR;Holtzman, DM
通讯作者：
Holtzman, DM