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推动脑类器官研究阿尔茨海默病的边界。

Pushing the boundaries of brain organoids to study Alzheimer's disease.

机构信息

Department of Neurodegenerative Diseases, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA; Irell and Manella Graduate School of Biological Sciences, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA.

SciNeuro Pharmaceuticals, Rockville, MD 20850, USA.

出版信息

Trends Mol Med. 2023 Aug;29(8):659-672. doi: 10.1016/j.molmed.2023.05.007. Epub 2023 Jun 21.


DOI:10.1016/j.molmed.2023.05.007
PMID:37353408
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10374393/
Abstract

Progression of Alzheimer's disease (AD) entails deterioration or aberrant function of multiple brain cell types, eventually leading to neurodegeneration and cognitive decline. Defining how complex cell-cell interactions become dysregulated in AD requires novel human cell-based in vitro platforms that could recapitulate the intricate cytoarchitecture and cell diversity of the human brain. Brain organoids (BOs) are 3D self-organizing tissues that partially resemble the human brain architecture and can recapitulate AD-relevant pathology. In this review, we highlight the versatile applications of different types of BOs to model AD pathogenesis, including amyloid-β and tau aggregation, neuroinflammation, myelin breakdown, vascular dysfunction, and other phenotypes, as well as to accelerate therapeutic development for AD.

摘要

阿尔茨海默病(AD)的进展涉及多种脑细胞类型的恶化或功能异常,最终导致神经退行性变和认知能力下降。定义 AD 中复杂的细胞-细胞相互作用如何失调需要新型的基于人类细胞的体外平台,这些平台可以再现人类大脑的复杂细胞结构和细胞多样性。脑类器官(BOs)是 3D 自组织组织,部分类似于人类大脑结构,可以再现与 AD 相关的病理学。在这篇综述中,我们强调了不同类型的 BOs 在模拟 AD 发病机制方面的多种应用,包括淀粉样蛋白-β和 tau 聚集、神经炎症、髓鞘破坏、血管功能障碍和其他表型,以及加速 AD 的治疗开发。

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本文引用的文献

[1]
APOE deficiency impacts neural differentiation and cholesterol biosynthesis in human iPSC-derived cerebral organoids.

Stem Cell Res Ther. 2023-8-21

[2]
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Nat Aging. 2023-3

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Nat Aging. 2022-11

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Nature. 2023-3

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APOE4 impairs myelination via cholesterol dysregulation in oligodendrocytes.

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Single cell transcriptomic profiling of a neuron-astrocyte assembloid tauopathy model.

Nat Commun. 2022-10-21

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