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诱导多能干细胞在阿尔茨海默病研究中的重要进展。

Important advances in Alzheimer's disease from the use of induced pluripotent stem cells.

机构信息

Brain Institute of Rio Grande do Sul (BraIns), Postgraduate Program in Medicine and Health Sciences (PUCRS), Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, 90610000, Brazil.

出版信息

J Biomed Sci. 2019 Feb 6;26(1):15. doi: 10.1186/s12929-019-0501-5.

DOI:10.1186/s12929-019-0501-5
PMID:30728025
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6366077/
Abstract

Among the various types of dementia, Alzheimer's disease (AD) is the most prevalent and is clinically defined as the appearance of progressive deficits in cognition and memory. Considering that AD is a central nervous system disease, getting tissue from the patient to study the disease before death is challenging. The discovery of the technique called induced pluripotent stem cells (iPSCs) allows to reprogram the patient's somatic cells to a pluripotent state by the forced expression of a defined set of transcription factors. Many studies have shown promising results and made important conclusions beyond AD using iPSCs approach. Due to the accumulating knowledge related to this topic and the important advances obtained until now, we review, using PubMed, and present an update of all publications related to AD from the use of iPSCs. The first iPSCs generated for AD were carried out in 2011 by Yahata et al. (PLoS One 6:e25788, 2011) and Yaqi et al. (Hum Mol Genet 20:4530-9, 2011). Like other authors, both authors used iPSCs as a pre-clinical tool for screening therapeutic compounds. This approach is also essential to model AD, testing early toxicity and efficacy, and developing a platform for drug development. Considering that the iPSCs technique is relatively recent, we can consider that the AD field received valuable contributions from iPSCs models, contributing to our understanding and the treatment of this devastating disorder.

摘要

在各种类型的痴呆症中,阿尔茨海默病(AD)最为常见,临床上定义为认知和记忆逐渐出现缺陷。鉴于 AD 是一种中枢神经系统疾病,在患者死亡前从患者身上获取组织来研究该疾病具有挑战性。诱导多能干细胞(iPSC)技术的发现,通过强制表达一组特定的转录因子,使患者的体细胞重编程为多能状态。许多研究使用 iPSC 方法取得了有希望的结果,并得出了超出 AD 的重要结论。由于与该主题相关的知识不断积累,以及迄今为止取得的重要进展,我们使用 PubMed 进行了回顾,并展示了从使用 iPSC 研究 AD 的所有出版物的更新。Yahata 等人(PLoS One 6:e25788, 2011)和 Yaqi 等人(Hum Mol Genet 20:4530-9, 2011)于 2011 年首次进行了用于 AD 的 iPSC 研究。与其他作者一样,两位作者都将 iPSC 用作筛选治疗化合物的临床前工具。这种方法对于模拟 AD、测试早期毒性和疗效以及开发药物开发平台也至关重要。考虑到 iPSC 技术相对较新,我们可以认为 AD 领域从 iPSC 模型中获得了有价值的贡献,有助于我们对这种破坏性疾病的理解和治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79e4/6366077/c0be8db30e6d/12929_2019_501_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79e4/6366077/c0be8db30e6d/12929_2019_501_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79e4/6366077/c0be8db30e6d/12929_2019_501_Fig1_HTML.jpg

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本文引用的文献

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Human fibroblast and stem cell resource from the Dominantly Inherited Alzheimer Network.来自显性遗传性阿尔茨海默病网络的人成纤维细胞和干细胞资源。
Alzheimers Res Ther. 2018 Jul 25;10(1):69. doi: 10.1186/s13195-018-0400-0.
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Generation of a human induced pluripotent stem cell-based model for tauopathies combining three microtubule-associated protein TAU mutations which displays several phenotypes linked to neurodegeneration.生成一种基于人诱导多能干细胞的 tau 病模型,该模型结合了三种微管相关蛋白 TAU 突变,表现出几种与神经退行性变相关的表型。
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人诱导多能干细胞在神经退行性疾病预测模型中的应用:梦想成真。
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Spinal Muscular Atrophy Modeling and Treatment Advances by Induced Pluripotent Stem Cells Studies.诱导多能干细胞研究在脊髓性肌萎缩症建模和治疗方面的进展。
Stem Cell Rev Rep. 2019 Dec;15(6):795-813. doi: 10.1007/s12015-019-09910-6.
The Impact of APP on Alzheimer-like Pathogenesis and Gene Expression in Down Syndrome iPSC-Derived Neurons.
APP 对唐氏综合征 iPSC 衍生神经元中阿尔茨海默病样发病机制和基因表达的影响。
Stem Cell Reports. 2018 Jul 10;11(1):32-42. doi: 10.1016/j.stemcr.2018.05.004. Epub 2018 May 31.
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Full-length amyloid precursor protein regulates lipoprotein metabolism and amyloid-β clearance in human astrocytes.全长淀粉样前体蛋白调节人星形胶质细胞中的脂蛋白代谢和淀粉样β清除。
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Common proteomic profiles of induced pluripotent stem cell-derived three-dimensional neurons and brain tissue from Alzheimer patients.诱导多能干细胞衍生的三维神经元和阿尔茨海默病患者脑组织的常见蛋白质组学特征。
J Proteomics. 2018 Jun 30;182:21-33. doi: 10.1016/j.jprot.2018.04.032. Epub 2018 Apr 27.
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Leptomeninges-Derived Induced Pluripotent Stem Cells and Directly Converted Neurons From Autopsy Cases With Varying Neuropathologic Backgrounds.尸检病例来源的软脑膜衍生诱导多能干细胞和直接转化神经元,具有不同的神经病理学背景。
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Oxidative stress and altered mitochondrial protein expression in the absence of amyloid-β and tau pathology in iPSC-derived neurons from sporadic Alzheimer's disease patients.散发性阿尔茨海默病患者诱导多能干细胞衍生神经元在无淀粉样β蛋白和tau蛋白病理情况下的氧化应激及线粒体蛋白表达改变
Stem Cell Res. 2018 Mar;27:121-130. doi: 10.1016/j.scr.2018.01.019. Epub 2018 Jan 28.
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Generation and characterization of human induced pluripotent stem cell (hiPSC) lines from an Alzheimer's disease (ASUi003-A) and non-demented control (ASUi004-A) patient homozygous for the Apolipoprotein e4 (APOE4) risk variant.从携带载脂蛋白E4(APOE4)风险变异纯合子的阿尔茨海默病患者(ASUi003 - A)和非痴呆对照患者(ASUi004 - A)中生成人类诱导多能干细胞(hiPSC)系并进行特征分析。
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Neurons derived from sporadic Alzheimer's disease iPSCs reveal elevated TAU hyperphosphorylation, increased amyloid levels, and GSK3B activation.源自散发性阿尔茨海默病 iPSC 的神经元显示出 TAU 过度磷酸化增加、淀粉样蛋白水平升高和 GSK3β 激活。
Alzheimers Res Ther. 2017 Dec 1;9(1):90. doi: 10.1186/s13195-017-0317-z.
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Establishment of induced pluripotent stem cell line (ZZUi010-A) from an Alzheimer's disease patient carrying an APP gene mutation.从一名携带APP基因突变的阿尔茨海默病患者建立诱导多能干细胞系(ZZUi010-A)。
Stem Cell Res. 2017 Dec;25:213-216. doi: 10.1016/j.scr.2017.10.025. Epub 2017 Nov 3.