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人诱导多能干细胞在阿尔茨海默病和 Tau 相关神经退行性疾病中的应用。

Human iPSC application in Alzheimer's disease and Tau-related neurodegenerative diseases.

机构信息

Department of Neuroscience, Ronald M. Loeb Center for Alzheimer's Disease, Icahn school of Medicine at Mount Sinai, New York, USA.

出版信息

Neurosci Lett. 2019 Apr 23;699:31-40. doi: 10.1016/j.neulet.2019.01.043. Epub 2019 Jan 24.

Abstract

Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by β-amyloid (Aβ) plaques and neurofibrillary tangles with progressive cognitive decline. After years of research with failed clinical trials surrounding Aβ and tau using numerous in vitro and in vivo AD transgenic animals, human model is necessary to advance our understanding of AD and drug discovery. Induced pluripotent stem cells (iPSCs) offers a novel approach for the establishment of a human model that reflects human genetics and physiology to investigate mechanisms of AD and other forms of dementia, which potentially could lead to a drug discovery, followed by treatment for the disease. In this review, I discuss the advantages in using iPSC technology with various forms of modeling, the progress that has been made to date in patient-derived AD iPSC model and challenges posed by using this technology. Finally, I suggest the future directions of disease modeling and the potential of iPSC technology in AD and other neurodegenerative research.

摘要

阿尔茨海默病(AD)是一种慢性神经退行性疾病,其特征是β-淀粉样蛋白(Aβ)斑块和神经原纤维缠结,伴有进行性认知能力下降。经过多年使用多种体外和体内 AD 转基因动物的失败临床试验研究 Aβ 和 tau 之后,人类模型对于深入了解 AD 和药物发现是必要的。诱导多能干细胞(iPSC)为建立反映人类遗传学和生理学的人类模型提供了一种新方法,用于研究 AD 和其他形式痴呆的机制,这可能会导致药物发现,随后对该疾病进行治疗。在这篇综述中,我讨论了使用 iPSC 技术进行各种形式建模的优势,以及迄今为止在患者来源的 AD iPSC 模型中取得的进展,以及使用该技术带来的挑战。最后,我提出了疾病建模的未来方向以及 iPSC 技术在 AD 和其他神经退行性研究中的潜力。

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