Modeling Alzheimer's disease: from past to future.
Modeling Alzheimer's disease: from past to future.
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DOI：
10.3389/fphar.2013.00077
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发表时间：
2013
影响因子：
5.6
通讯作者：
Di Luca M
中科院分区：
文献类型：
--
作者：
Saraceno C;Musardo S;Marcello E;Pelucchi S;Di Luca M
随着越来越多的人寿命足够长，阿尔茨海默病（AD）正在成为老年人中最普遍和最具社会破坏性的疾病。尽管阿尔茨海默病给社会带来了相当大的负担，而且负担越来越重，但它代表了神经学领域最大的未满足的医疗需求，因为目前的药物可以改善症状，但没有深刻的疾病改善作用。尽管阿尔茨海默病的发病机制是多方面的，难以确定，但遗传学和细胞生物学的研究导致了淀粉样蛋白假说，该假说认为淀粉样蛋白β (a β)在阿尔茨海默病的发病机制中起着关键作用。淀粉样前体蛋白（APP）以及β-和γ-分泌酶是Aβ生成的主要参与者，而α-分泌酶在APP上的裂解可阻止Aβ的沉积。早发性家族性AD与APP和γ-分泌酶组分突变的关联为建立该疾病的动物模型提供了一个潜在的工具。然而，一个概括AD所有方面的模型尚未产生。在这里，我们面临的问题是建立AD病理模型，描述几个模型，这些模型在定义关键疾病相关机制和探索新的潜在治疗方法中发挥了重要作用。特别是，我们将广泛概述不同AD模型的不同特征和优缺点，从无脊椎动物模型到啮齿动物模型，最后处理计算模型和诱导多能干细胞。
Alzheimer’s disease (AD) is emerging as the most prevalent and socially disruptive illness of aging populations, as more people live long enough to become affected. Although AD is placing a considerable and increasing burden on society, it represents the largest unmet medical need in neurology, because current drugs improve symptoms, but do not have profound disease-modifying effects. Although AD pathogenesis is multifaceted and difficult to pinpoint, genetic and cell biological studies led to the amyloid hypothesis, which posits that amyloid β (Aβ) plays a pivotal role in AD pathogenesis. Amyloid precursor protein (APP), as well as β- and γ-secretases are the principal players involved in Aβ production, while α-secretase cleavage on APP prevents Aβ deposition. The association of early onset familial AD with mutations in the APP and γ-secretase components provided a potential tool of generating animal models of the disease. However, a model that recapitulates all the aspects of AD has not yet been produced. Here, we face the problem of modeling AD pathology describing several models, which have played a major role in defining critical disease-related mechanisms and in exploring novel potential therapeutic approaches. In particular, we will provide an extensive overview on the distinct features and pros and contras of different AD models, ranging from invertebrate to rodent models and finally dealing with computational models and induced pluripotent stem cells.
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影响因子：
4.2
作者：
Boncristiano, S;Calhoun, ME;Jucker, M
通讯作者：
Jucker, M
影响因子：
64.8
作者：
Chen, GQ;Chen, KS;Morris, RGM
通讯作者：
Morris, RGM
影响因子：
4.2
作者：
Andra, K;Abramowski, D;Staufenbiel, M
通讯作者：
Staufenbiel, M
影响因子：
25
作者：
Chapman, PF;White, GL;Hsiao, KK
通讯作者：
Hsiao, KK
DOI：
10.1037/h0077579
发表时间：
1979-01-01
期刊：
JOURNAL OF COMPARATIVE AND PHYSIOLOGICAL PSYCHOLOGY
影响因子：
--
作者：
BARNES, CA
通讯作者：
BARNES, CA