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利用人类细胞衍生的脑类器官和3D模型模拟阿尔茨海默病。

Modeling Alzheimer's disease using human cell derived brain organoids and 3D models.

作者信息

Fernandes Sarah, Revanna Jasmin, Pratt Joshua, Hayes Nicholas, Marchetto Maria C, Gage Fred H

机构信息

Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA, United States.

Department of Biological Sciences, University of California, San Diego, La Jolla, CA, United States.

出版信息

Front Neurosci. 2024 Aug 1;18:1434945. doi: 10.3389/fnins.2024.1434945. eCollection 2024.


DOI:10.3389/fnins.2024.1434945
PMID:39156632
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11328153/
Abstract

Age-related neurodegenerative diseases, like Alzheimer's disease (AD), are challenging diseases for those affected with no cure and limited treatment options. Functional, human derived brain tissues that represent the diverse genetic background and cellular subtypes contributing to sporadic AD (sAD) are limited. Human stem cell derived brain organoids recapitulate some features of human brain cytoarchitecture and AD-like pathology, providing a tool for illuminating the relationship between AD pathology and neural cell dysregulation leading to cognitive decline. In this review, we explore current strategies for implementing brain organoids in the study of AD as well as the challenges associated with investigating age-related brain diseases using organoid models.

摘要

与年龄相关的神经退行性疾病,如阿尔茨海默病(AD),对于患者来说是极具挑战性的疾病,因为尚无治愈方法且治疗选择有限。能够代表导致散发性AD(sAD)的多种遗传背景和细胞亚型的功能性人类衍生脑组织非常有限。人类干细胞衍生的脑类器官概括了人类脑细结构和AD样病理学的一些特征,为阐明AD病理学与导致认知衰退的神经细胞失调之间的关系提供了一种工具。在这篇综述中,我们探讨了在AD研究中应用脑类器官的当前策略,以及使用类器官模型研究与年龄相关的脑部疾病所面临的挑战。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19c6/11328153/f279dadb03a5/fnins-18-1434945-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19c6/11328153/8fb2d500058e/fnins-18-1434945-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19c6/11328153/fc4b3dd634bd/fnins-18-1434945-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19c6/11328153/f279dadb03a5/fnins-18-1434945-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19c6/11328153/8fb2d500058e/fnins-18-1434945-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19c6/11328153/fc4b3dd634bd/fnins-18-1434945-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19c6/11328153/f279dadb03a5/fnins-18-1434945-g003.jpg

相似文献

[1]
Modeling Alzheimer's disease using human cell derived brain organoids and 3D models.

Front Neurosci. 2024-8-1

[2]
Modeling Sporadic Alzheimer's Disease in Human Brain Organoids under Serum Exposure.

Adv Sci (Weinh). 2021-9

[3]
Modeling Neurodegenerative Microenvironment Using Cortical Organoids Derived from Human Stem Cells.

Tissue Eng Part A. 2018-2-27

[4]
Modeling APOE ε4 familial Alzheimer's disease in directly converted 3D brain organoids.

Front Aging Neurosci. 2024-8-9

[5]
Modeling Alzheimer's Disease Using Human Brain Organoids.

Methods Mol Biol. 2023

[6]
Modelling Alzheimer's disease using human brain organoids: current progress and challenges.

Expert Rev Mol Med. 2022-12-15

[7]
Pushing the boundaries of brain organoids to study Alzheimer's disease.

Trends Mol Med. 2023-8

[8]
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Front Pharmacol. 2020-3-31

[9]
Current progress of cerebral organoids for modeling Alzheimer's disease origins and mechanisms.

Bioeng Transl Med. 2022-8-2

[10]
Enhanced Neuronal Activity and Asynchronous Calcium Transients Revealed in a 3D Organoid Model of Alzheimer's Disease.

ACS Biomater Sci Eng. 2021-1-11

引用本文的文献

[1]
A human neuron alzheimer's disease model reveals barriers to senolytic translatability.

Alzheimers Res Ther. 2025-7-26

[2]
Experimental modeling of Alzheimer's disease: Translational lessons from cross-taxon analyses.

Alzheimers Dement. 2025-5

[3]
Emerging Insights into Brain Inflammation: Stem-Cell-Based Approaches for Regenerative Medicine.

Int J Mol Sci. 2025-4-1

[4]
Cell reprogramming: methods, mechanisms and applications.

Cell Regen. 2025-3-27

[5]
Age-Related Neurodegenerative Diseases: A Stem Cell's Perspective.

Cells. 2025-2-27

本文引用的文献

[1]
APOE4 homozygozity represents a distinct genetic form of Alzheimer's disease.

Nat Med. 2024-5

[2]
APOE4/4 is linked to damaging lipid droplets in Alzheimer's disease microglia.

Nature. 2024-4

[3]
Morphological diversification and functional maturation of human astrocytes in glia-enriched cortical organoid transplanted in mouse brain.

Nat Biotechnol. 2025-1

[4]
iPS-cell-derived microglia promote brain organoid maturation via cholesterol transfer.

Nature. 2023-11

[5]
Transcriptomic and morphological maturation of human astrocytes in cerebral organoids.

Glia. 2024-2

[6]
Species-specific metabolic reprogramming in human and mouse microglia during inflammatory pathway induction.

Nat Commun. 2023-10-13

[7]
An in vivo neuroimmune organoid model to study human microglia phenotypes.

Cell. 2023-5-11

[8]
Microglia-mediated T cell infiltration drives neurodegeneration in tauopathy.

Nature. 2023-3

[9]
Amyloid beta accumulations and enhanced neuronal differentiation in cerebral organoids of Dutch-type cerebral amyloid angiopathy patients.

Front Aging Neurosci. 2023-1-17

[10]
Benchmarking brain organoid recapitulation of fetal corticogenesis.

Transl Psychiatry. 2022-12-20

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