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On-line Access: 2024-08-27

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 ORCID:

Xintai WANG

https://orcid.org/0000-0001-9328-7220

Ying SHEN

https://orcid.org/0000-0001-7034-5328

Zhijie LIN

https://orcid.org/0009-0006-3824-5937

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Journal of Zhejiang University SCIENCE B 2024 Vol.25 No.10 P.878-889

http://doi.org/10.1631/jzus.B2300712


Perspectives in the investigation of Cockayne syndrome group B neurological disease: the utility of patient-derived brain organoid models


Author(s):  Xintai WANG, Rui ZHENG, Marina DUKHINOVA, Luxi WANG, Ying SHEN, Zhijie LIN

Affiliation(s):  Zhejiang Key Laboratory of Organ Development and Regeneration, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou 311121, China; more

Corresponding email(s):   linzj@hznu.edu.cn, yshen@zju.edu.cn

Key Words:  Cockayne syndrome, Cockayne syndrome group B (CSB), Neurological function, Cerebellum, Organoids


Xintai WANG, Rui ZHENG, Marina DUKHINOVA, Luxi WANG, Ying SHEN, Zhijie LIN. Perspectives in the investigation of Cockayne syndrome group B neurological disease: the utility of patient-derived brain organoid models[J]. Journal of Zhejiang University Science B, 2024, 25(10): 878-889.

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journal="Journal of Zhejiang University Science B",
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A1 - Ying SHEN
A1 - Zhijie LIN
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Abstract: 
cockayne syndrome (CS) group B (CSB), which results from mutations in the excision repair cross-complementation group 6 (ERCC6) genes, which produce CSB protein, is an autosomal recessive disease characterized by multiple progressive disorders including growth failure, microcephaly, skin photosensitivity, and premature aging. Clinical data show that brain atrophy, demyelination, and calcification are the main neurological manifestations of CS, which progress with time. Neuronal loss and calcification occur in various brain areas, particularly the cerebellum and basal ganglia, resulting in dyskinesia, ataxia, and limb tremors in CSB patients. However, the understanding of neurodevelopmental defects in CS has been constrained by the lack of significant neurodevelopmental and functional abnormalities observed in CSB-deficient mice. In this review, we focus on elucidating the protein structure and distribution of CSB and delve into the impact of CSB mutations on the development and function of the nervous system. In addition, we provide an overview of research models that have been instrumental in exploring CS disorders, with a forward-looking perspective on the substantial contributions that brain organoids are poised to further advance this field.

Cockayne综合征B神经系统病变研究展望: 患者来源的脑类器官模型的应用

王新泰1, 郑芮2,3, 玛瑞娜·杜希诺娃3,4, 王露曦3, 沈颖3, 林智杰1
1杭州师范大学生命与环境科学学院, 浙江省器官发育与再生重点实验室, 中国杭州市, 311121
2浙江大学医学院附属儿童医院, 国家儿童健康与疾病临床医学研究中心, 中国杭州市, 310052
3浙江大学医学院生理学系, 中国杭州市, 310058
4浙江大学第四医院 / 一带一路国际医学院国际医学健康研究院, 中国义乌市, 322001
摘要:Cockayne综合征B(CSB)作为一种常染色体隐性遗传病,由ERCC6基因(编码CSB蛋白)突变引起,患者表现为生长迟缓、小头畸形、皮肤光敏性和早衰等。临床证据表明,CSB神经系统病变主要表现为脑萎缩、脱髓鞘和脑部钙化,并随时间推移愈发严重。神经元丢失和钙化可发生在各个脑区,其中小脑和基底神经节的神经元丢失和钙化最为严重,是导致CSB患者运动障碍、共济失调和肢体震颤的主因之一。目前CSB蛋白缺失小鼠并不能重现患者神经系统发育和功能异常,这是制约探究Cockayne综合征神经系统病变机制的主要因素。本文综述了CSB的蛋白结构和表达分布,总结探讨了CSB突变对神经系统发育和功能的影响,概述了目前研究Cockayne综合征的模式生物,并前瞻性地讨论了利用患者来源的脑类器官应用于研究Cockayne综合征神经系统病变的潜在价值。

关键词:Cockayne综合征;Cockayne综合征B(CSB);神经系统功能;小脑;脑类器官

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

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