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诱导多能干细胞治疗和模拟阿尔茨海默病的潜力

The Potential of Induced Pluripotent Stem Cells to Treat and Model Alzheimer's Disease.

作者信息

Schulz Joseph M

机构信息

Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando FL 32816, USA.

出版信息

Stem Cells Int. 2021 May 26;2021:5511630. doi: 10.1155/2021/5511630. eCollection 2021.

Abstract

An estimated 6.2 million Americans aged 65 or older are currently living with Alzheimer's disease (AD), a neurodegenerative disease that disrupts an individual's ability to function independently through the degeneration of key regions in the brain, including but not limited to the hippocampus, the prefrontal cortex, and the motor cortex. The cause of this degeneration is not known, but research has found two proteins that undergo posttranslational modifications: tau, a protein concentrated in the axons of neurons, and amyloid precursor protein (APP), a protein concentrated near the synapse. Through mechanisms that have yet to be elucidated, the accumulation of these two proteins in their abnormal aggregate forms leads to the neurodegeneration that is characteristic of AD. Until the invention of induced pluripotent stem cells (iPSCs) in 2006, the bulk of research was carried out using transgenic animal models that offered little promise in their ability to translate well from benchtop to bedside, creating a bottleneck in the development of therapeutics. However, with iPSC, patient-specific cell cultures can be utilized to create models based on human cells. These human cells have the potential to avoid issues in translatability that have plagued animal models by providing researchers with a model that closely resembles and mimics the neurons found in humans. By using human iPSC technology, researchers can create more accurate models of AD while also focusing on regenerative medicine using iPSC . The following review focuses on the current uses of iPSC and how they have the potential to regenerate damaged neuronal tissue, in the hopes that these technologies can assist in getting through the bottleneck of AD therapeutic research.

摘要

据估计,目前有620万65岁及以上的美国人患有阿尔茨海默病(AD),这是一种神经退行性疾病,通过大脑关键区域(包括但不限于海马体、前额叶皮质和运动皮质)的退化,破坏个体独立生活的能力。这种退化的原因尚不清楚,但研究发现了两种经过翻译后修饰的蛋白质:tau蛋白,一种集中在神经元轴突中的蛋白质,以及淀粉样前体蛋白(APP),一种集中在突触附近的蛋白质。通过尚未阐明的机制,这两种蛋白质以其异常聚集形式的积累导致了AD特有的神经退行性变。在2006年诱导多能干细胞(iPSC)发明之前,大部分研究是使用转基因动物模型进行的,这些模型在从实验室到临床的转化能力方面前景渺茫,在治疗方法的开发中造成了瓶颈。然而,有了iPSC,可以利用患者特异性细胞培养物来创建基于人类细胞的模型。这些人类细胞有可能避免困扰动物模型的可转化性问题,为研究人员提供一个与人类神经元非常相似并能模拟人类神经元的模型。通过使用人类iPSC技术,研究人员可以创建更准确的AD模型,同时也专注于利用iPSC进行再生医学研究。以下综述重点介绍了iPSC的当前用途以及它们如何有可能再生受损的神经元组织,希望这些技术有助于突破AD治疗研究的瓶颈。

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