The Impact of the Cellular Environment and Aging on Modeling Alzheimer's Disease in 3D Cell Culture Models.
The Impact of the Cellular Environment and Aging on Modeling Alzheimer's Disease in 3D Cell Culture Models.
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DOI：
10.1002/advs.202205037
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发表时间：
2023-03
期刊：
影响因子：
15.1
通讯作者：
Kim, Doo Yeon
中科院分区：
文献类型：
--
作者：
Hebisch, Matthias;Klostermeier, Stefanie;Wolf, Katharina;Boccaccini, Aldo R.;Wolf, Stephan E.;Tanzi, Rudolph E.;Kim, Doo Yeon
创建准确概括疾病病理学的阿尔茨海默病 (AD) 细胞模型一直是一项长期挑战。最近的研究表明，整合到三维 (3D) 水凝胶基质中的人类 AD 神经细胞显示出 AD 神经病理学的关键特征。与人脑一样，细胞外基质 (ECM) 在确定基于水凝胶的 3D 细胞模型中的神经发病率方面发挥着关键作用。衰老是 AD 的最大危险因素，它会显着改变大脑 ECM 特性。因此，了解与年龄相关的 ECM 变化如何影响 AD 患者和体外模型中致病分子的积累、神经炎症和神经变性非常重要。 在这篇综述中，提出了机制假设来解决 ECM 特性及其随衰老而变化对 AD 和 AD 相关痴呆的影响。老年大脑中 ECM 特征的改变，包括基质硬度、孔径和成分，将通过调节 AD 致病分子的积累、传播和传播来促进疾病的发病机制。具有不同 ECM 特性的新兴水凝胶疾病模型为研究大脑 ECM 老化对 AD 发病机制的影响提供了令人兴奋的机会，并提供了新的机制见解。了解 ECM 老化在 AD 发病机制中的作用也应该可以改善 3D 水凝胶系统中 AD 的建模。新兴的基于水凝胶的 3D 神经细胞培养模型为研究大脑细胞外基质 (ECM) 及其衰老对阿尔茨海默病 (AD) 发病机制的影响提供了令人兴奋的机会。老年大脑中 ECM 特征的改变通过调节 AD 致病分子的积累、传播和传播来促进疾病的发病机制。了解 ECM 老化的致病作用也将改善培养皿中 AD 的建模。
Creating a cellular model of Alzheimer's disease (AD) that accurately recapitulates disease pathology has been a longstanding challenge. Recent studies showed that human AD neural cells, integrated into three‐dimensional (3D) hydrogel matrix, display key features of AD neuropathology. Like in the human brain, the extracellular matrix (ECM) plays a critical role in determining the rate of neuropathogenesis in hydrogel‐based 3D cellular models. Aging, the greatest risk factor for AD, significantly alters brain ECM properties. Therefore, it is important to understand how age‐associated changes in ECM affect accumulation of pathogenic molecules, neuroinflammation, and neurodegeneration in AD patients and in vitro models. In this review, mechanistic hypotheses is presented to address the impact of the ECM properties and their changes with aging on AD and AD‐related dementias. Altered ECM characteristics in aged brains, including matrix stiffness, pore size, and composition, will contribute to disease pathogenesis by modulating the accumulation, propagation, and spreading of pathogenic molecules of AD. Emerging hydrogel‐based disease models with differing ECM properties provide an exciting opportunity to study the impact of brain ECM aging on AD pathogenesis, providing novel mechanistic insights. Understanding the role of ECM aging in AD pathogenesis should also improve modeling AD in 3D hydrogel systems. Emerging hydrogel‐based 3D neural cell culture models provide an exciting opportunity to study the impact of brain extracellular matrix (ECM) and its aging on Alzheimer's disease (AD) pathogenesis. Altered ECM characteristics in aged brains contribute to disease pathogenesis by modulating the accumulation, propagation, and spreading of pathogenic molecules of AD. Understanding the pathogenic role of ECM aging will also improve modeling AD in a dish.
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DOI：
10.1073/pnas.0812227106
发表时间：
2009-05-12
影响因子：
11.1
作者：
Carullaa, Natalia;Zhou, Min;Dobson, Christopher M.
通讯作者：
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影响因子：
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DOI：
10.1016/j.bbapap.2013.08.010
发表时间：
2013-12-01
影响因子：
3.2
作者：
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影响因子：
82.9
作者：
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影响因子：
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作者：
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