人类中脑类器官：用于高级帕金森病建模和治疗探索的强大工具-动脉网

Human midbrain organoids: a powerful tool for advanced Parkinson’s disease modeling and therapy exploration

Nature 等信源发布 2024-10-20 00:46

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AbstractParkinson’s disease (PD) is a neurodegenerative disorder marked by the loss of dopaminergic neurons in the substantia nigra. Despite progress, the pathogenesis remains unclear. Human midbrain organoids (hMLOs) have emerged as a promising model for studying PD, drug screening, and potential treatments.

摘要帕金森病（PD）是一种以黑质多巴胺能神经元丢失为特征的神经退行性疾病。尽管取得了进展，但发病机制仍不清楚。人类中脑类器官（hMLOs）已成为研究PD，药物筛选和潜在治疗的有前途的模型。

This review discusses the development of hMLOs, their application in PD research, and current challenges in organoid construction, highlighting possible optimization strategies..

这篇综述讨论了hMLOs的发展，它们在PD研究中的应用，以及类器官构建中当前的挑战，突出了可能的优化策略。。

IntroductionParkinson’s disease (PD) is one of the most common neurodegenerative disorders associated with movement disabilities, affecting more than 6.1 million people worldwide1,2, with the mean age of onset at 553. Clinically, as a debilitating neurological disorder, PD patients mainly present with motor symptoms such as resting tremor, bradykinesia, rigidity, postural instability, loss of coordination and shuffling or freezing gait4,5,6.

引言帕金森病（PD）是与运动障碍相关的最常见的神经退行性疾病之一，影响全球610多万人1,2，平均发病年龄为553岁。临床上，作为一种使人衰弱的神经系统疾病，PD患者主要表现为运动症状，如静息性震颤，运动迟缓，僵硬，姿势不稳，协调丧失以及改组或僵硬4,5,6。

Non-motor symptoms may also present including depression, anxiety, constipation, sleep disturbances, hyposmia, paresthesia, and cognitive abnormalities7,8,9,10. The key histopathological hallmark of PD is the gradual loss of midbrain dopaminergic (mDA) neurons and the presence of intraneuronal protein inclusions named “Lewy Bodies” (LB) in substantia nigra (SN)3,10,11,12.

。PD的关键组织病理学标志是中脑多巴胺能（mDA）神经元的逐渐丧失以及黑质（SN）3,10,11,12中存在称为“路易体”（LB）的神经内蛋白质内含物。

Composed of abnormal α-synuclein (α-syn) protein aggregations13, LBs-associated pathology has been attributed to mitochondrial metabolism alteration and proteasomal and autophagy-lysosomal dysregulation, which ultimately bring about the death of mDA14,15.Up to now, there are three prevalent tools to explore the underlying mechanism of PD, including the post-mortem brain tissue from PD patients, animal models and in vitro cell models.

LBs相关病理学由异常的α-突触核蛋白（α-syn）蛋白聚集13组成，归因于线粒体代谢改变以及蛋白酶体和自噬溶酶体失调，最终导致mDA14的死亡，15。到目前为止，有三种流行的工具来探索PD的潜在机制，包括PD患者的死后脑组织，动物模型和体外细胞模型。

The post-mortem brain of PD patient is an ideal source for the PD analysis which directly reflect the actual inner environment. The use of human brain tissue, however, is strictly restricted by practical constraints16,17,18,19,20,21. Furthermore, post-mortem brain tissue may have undergone irreversible changes during the process of death that limit its utility for the study of PD16.

PD患者的死后脑是PD分析的理想来源，它直接反映了实际的内部环境。然而，人脑组织的使用受到实际限制16,17,18,19,20,21的严格限制。此外，死后脑组织在死亡过程中可能发生了不可逆转的变化，这限制了其在PD16研究中的应用。

Animal models of PD can be further divided into two groups, the toxin-based model and gene-based model3. By introducing neurotoxins such as 6-hydroxydopami.

PD的动物模型可以进一步分为两组，基于毒素的模型和基于基因的模型3。通过引入神经毒素，例如6-羟基多巴。

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Download referencesAcknowledgementsThe authors’ work was supported by the National Natural Science Foundation of China (82271277 to C.M.), and the Innovative and Scientific and Technological Talent Training Project of Henan Province (Grant YXKC2021062 to C.M.), and the Non-profit Central Research Institute Fund of Chinses Academy of Medical Sciences (2020-PT310-01 to Y.X.).Author informationAuthor notesThese authors contributed equally: Xin Cui, Xinwei Li, Huimin Zheng, Yun Su.Authors and AffiliationsDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, ChinaXin Cui, Xinwei Li, Huimin Zheng, Yun Su, Shuyu Zhang, Mengjie Li, Xiaoyan Hao, Shuo Zhang, Zhengwei Hu, Zongping Xia, Changhe Shi, Yuming Xu & Chengyuan MaoAcademy of Medical Sciences of Zhengzhou University, Zhengzhou, ChinaXin Cui, Xinwei Li, Shuo Zhang & Zhengwei HuHenan Key Laboratory of Cerebrovascular Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, ChinaXin Cui, Xinwei Li, Huimin Zheng, Yun Su, Mengjie Li, Xiaoyan Hao, Shuo Zhang, Zhengwei Hu, Zongping Xia, Changhe Shi, Yuming Xu & Chengyuan MaoNeuro-Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaShuyu ZhangClinical Systems Biology Laboratories, Zhengzhou University, Zhengzhou, ChinaZongping XiaInstitute of Neuroscience, Zhengzhou University, Zhengzhou, ChinaChanghe Shi & Yuming XuAuthorsXin CuiView author publicationsYou can also search for this author in.

下载参考文献致谢作者的工作得到了国家自然科学基金（82271277至C.M.）和河南省创新科技人才培养项目（YXKC2021062至C.M.）以及中国医学科学院非营利性中央研究所基金（2020-PT310-01至Y.X.）的支持。作者信息作者注意到这些作者做出了同样的贡献：崔欣，李新伟，郑惠民，苏云。作者和所属单位郑州大学第一附属医院神经内科，郑州，中国崔欣，李新伟，郑惠民，苏云，张舒宇，李孟杰，郝晓燕，张硕，胡正伟，夏宗平，石昌河，徐玉明，程源毛泽东郑州大学医学科学院，郑州，崔欣，李新伟，张硕，胡正伟河南脑血管疾病重点实验室，郑州大学第一附属医院，郑州大学，崔新新，崔新伟，张硕，胡正伟，河南省脑血管疾病重点实验室，郑州大学，郑州，崔新新，崔新新，郑新民，郑新民，郑新民，郑新民，郑新民，郑新民，郑新民，郑，中国郑州大学夏宗平神经科学研究所，郑州，中国常河市和徐玉明作者Xin CuiView作者出版物您也可以在中搜索这位作者。

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PubMed Google ScholarContributionsXin Cui, Xinwei Li, Huimin Zheng and Yun Su drafted and revised of the manuscript for content, including medical writing for the content. Changhe Shi, Shuyu Zhang, Mengjie Li, Xiaoyan Hao, Shuo Zhang, Zhengwei Hu, Zongping Xia and Changhe Shi assembled and edited the figures and tables.

PubMed谷歌学术贡献Xin Cui，Xinwei Li，Huimin Zheng和Yun Su起草并修订了手稿的内容，包括内容的医学写作。石昌和、张淑玉、李梦洁、郝晓燕、张硕、胡正伟、夏宗平和石昌和组装并编辑了这些数字和表格。

Chengyuan Mao and Yuming Xu conceived the manuscript.Corresponding authorsCorrespondence to.

毛承元和徐玉明构思了手稿。通讯作者通讯。

Yuming Xu or Chengyuan Mao.Ethics declarations

徐玉明或毛成元。道德宣言

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Reprints and permissionsAbout this articleCite this articleCui, X., Li, X., Zheng, H. et al. Human midbrain organoids: a powerful tool for advanced Parkinson’s disease modeling and therapy exploration.

转载和许可本文引用本文Cui，X.，Li，X.，Zheng，H。等人。人类中脑类器官：用于晚期帕金森病建模和治疗探索的有力工具。

npj Parkinsons Dis. 10, 189 (2024). https://doi.org/10.1038/s41531-024-00799-8Download citationReceived: 06 January 2023Accepted: 02 October 2024Published: 20 October 2024DOI: https://doi.org/10.1038/s41531-024-00799-8Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

npj帕金森病。10189（2024）。https://doi.org/10.1038/s41531-024-00799-8Download引文收到日期：2023年1月6日接受日期：2024年10月2日发布日期：2024年10月20日OI：https://doi.org/10.1038/s41531-024-00799-8Share本文与您共享以下链接的任何人都可以阅读此内容：获取可共享链接对不起，本文目前没有可共享的链接。复制到剪贴板。

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