Familial Alzheimer's disease modelling using induced pluripotent stem cell technology.
Familial Alzheimer's disease modelling using induced pluripotent stem cell technology.
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DOI：
10.4252/wjsc.v6.i2.239
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发表时间：
2014-04-26
影响因子：
4.1
通讯作者：
Ward, Christopher M
中科院分区：
文献类型：
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作者：
Mohamet, Lisa;Miazga, Natalie J;Ward, Christopher M
阿尔茨海默氏病（AD）是一种进行性神经退行性疾病，其中患者表现出逐渐丧失记忆，损害他们学习或执行日常任务的能力。AD的诊断是困难的，特别是在疾病的早期阶段，主要包括认知评估，只有四分之一的患者被正确诊断。用于治疗AD的新型疗法的开发已被证明是一个漫长、昂贵且相对低效的过程，损耗率> 90%。因此，没有治愈AD的方法，患者可用的治疗选择很少。因此，迫切需要能够准确且可再现地模拟AD表型并且适合于高含量筛选应用的药物发现平台。在这里，我们讨论了使用诱导多能干细胞（iPSC），它可以来自成人细胞，作为体外重现AD表型的方法。我们评估了它们在高含量筛选试验中的潜在用途，以及实现其在预测疗效、毒理学和疾病建模方面的全部潜力所存在的障碍。目前，在使用iPSC技术完全实现AD治疗应用之前，需要解决许多限制。然而，虽然在药物发现中使用AD衍生的iPSC仍然是一个新兴领域，但它具有巨大的潜力，可能在未来几年内实现。
Alzheimer's disease (AD) is a progressive neurodegenerative disease in which patients exhibit gradual loss of memory that impairs their ability to learn or carry out daily tasks. Diagnosis of AD is difficult, particularly in early stages of the disease, and largely consists of cognitive assessments, with only one in four patients being correctly diagnosed. Development of novel therapeutics for the treatment of AD has proved to be a lengthy, costly and relatively unproductive process with attrition rates of > 90%. As a result, there are no cures for AD and few treatment options available for patients. Therefore, there is a pressing need for drug discovery platforms that can accurately and reproducibly mimic the AD phenotype and be amenable to high content screening applications. Here, we discuss the use of induced pluripotent stem cells (iPSCs), which can be derived from adult cells, as a method of recapitulation of AD phenotype in vitro. We assess their potential use in high content screening assays and the barriers that exist to realising their full potential in predictive efficacy, toxicology and disease modelling. At present, a number of limitations need to be addressed before the use of iPSC technology can be fully realised in AD therapeutic applications. However, whilst the use of AD-derived iPSCs in drug discovery remains a fledgling field, it is one with immense potential that is likely to reach fruition within the next few years.