长链非编码RNA在阿尔茨海默病中的研究进展

doi:10.16288/j.yczz.21-427

遗传 ›› 2022, Vol. 44 ›› Issue (3): 189-197.doi: 10.16288/j.yczz.21-427

长链非编码RNA在阿尔茨海默病中的研究进展

熊婉迪¹(), 徐开宇⁴, 陆林^1,³, 李家立^2,⁴()

1. 北京大学前沿交叉学科研究院生命联合中心,北京 100091
2. 北京大学中国药物依赖性研究所,北京 100191
3. 北京大学第六医院,北京 100191
4. 中国科学院昆明动物研究所, 中国科学院&云南省动物模型与人类疾病机理重点实验室,昆明 650223;

收稿日期:2021-12-20 修回日期:2022-01-21 出版日期:2022-03-20 发布日期:2022-02-16
通讯作者: 李家立 E-mail:wandibear@pku.edu.cn;lijiali@mail.kiz.ac.cn
作者简介:熊婉迪,在读博士研究生,研究方向：神经生物学。E-mail: wandibear@pku.edu.cn
基金资助:
国家自然科学基金项目资助(81761128036)

Research progress on lncRNAs in Alzheimer’s disease

Wandi Xiong¹(), Kaiyu Xu⁴, Lin Lu^1,³, Jiali Li^2,⁴()

1. Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100091, China
2. National Institute on Drug Dependence, Peking University, Beijing 100191, China
3. Peking University Sixth Hospital, Peking University, Beijing 100191, China
4. Key Laboratory of Animal Models and Human Disease Mechanism of Chinese Academy of Science & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China;

Received:2021-12-20 Revised:2022-01-21 Online:2022-03-20 Published:2022-02-16
Contact: Li Jiali E-mail:wandibear@pku.edu.cn;lijiali@mail.kiz.ac.cn
Supported by:
Supported by the National Natural Science Foundation of China(81761128036)

摘要/Abstract

摘要：

阿尔茨海默病(Alzheimer's disease, AD)是常见的神经退行性疾病,也是最为常见的一类老年痴呆类型。AD主要的病理变化包括淀粉样蛋白(amyloid-β, Aβ)沉积、tau蛋白过度磷酸化、胆碱能神经元的缺失、神经炎症以及代谢障碍等。然而,有关AD具体的发病机制和分子谱尚不清楚,这给AD的诊断和治疗带来很大的挑战。越来越多的研究发现,长链非编码RNA (long non-coding RNAs, lncRNAs)在AD发病机制中发挥着重要作用。本文就lncRNAs在AD的研究进展,从lncRNAs通过影响Aβ聚积、突触功能、炎症反应和线粒体功能等方面参与AD的发病来展开综述介绍,为AD早期诊断的生物标志物和药物治疗靶点提供新思路。

关键词: 长链非编码RNA, 阿尔茨海默病, β淀粉样蛋白, 突触功能

Abstract:

Alzheimer’s disease (AD) is the common neurodegenerative disease in the center never system and the typical dementia in old people. The major pathological changes of AD are the accumulation of amyloid-β (Aβ) plaques, neurofibrillary tangles, loss of cholinergic neurons, inflammation and metabolism dysfunction. However, the molecular mechanism leading to AD pathogenesis is not clear. More and more studies reported that long non-coding RNAs (lncRNAs) play important roles in AD. In this review, we briefly introduce the recent research progress on lncRNAs in AD, including their regulation of clearance of the Aβ plaques, synaptic function, inflammation reaction and mitochondrial function, and thus providing the references for that lncRNAs can serve as a potential diagnostic biomarker and therapeutic target in AD.

Key words: lncRNA, Alzheimer’s disease, amyloid-β, synaptic function

熊婉迪, 徐开宇, 陆林, 李家立. 长链非编码RNA在阿尔茨海默病中的研究进展[J]. 遗传, 2022, 44(3): 189-197.

Wandi Xiong, Kaiyu Xu, Lin Lu, Jiali Li. Research progress on lncRNAs in Alzheimer’s disease[J]. Hereditas(Beijing), 2022, 44(3): 189-197.

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名称	表达	作用机制	实验模型	参考文献
BACE1-AS	↑	提高BACE1 mRNA稳定性,增加Aβ₄₂聚积	细胞系,Tg19959小鼠	[20]
51A	↑	下调SORL1,增加Aβ₄₂的聚积	细胞系	[34]
BC200	↑	调控突触后膜局部蛋白质,影响突触功能	AD患者人脑	[24]
BDNF-AS	↑	减少BDNF的表达,神经营养物质耗竭	细胞系,小鼠脑区注射 Aβ₄₂	[35]
NDM29	↑	促进BACE分泌酶的剪切活性,增加Aβ₄₂聚积	细胞系	[31]
17A	↑	影响GABA B信号通路,增加Aβ₄₂的聚积	细胞系	[33]
NEAT1	↑	结合NEDD4L促进PINK1降解,影响线粒体自噬	细胞系,APP/PS1小鼠	[36]
EBF3-AS	↑	促进EBF3上调,促进神经元凋亡	细胞系,APP/PS1小鼠	[37]
SOX21-AS1	↑	上调FZD3/5激活Wnt信号通路,调控突触功能	小鼠脑区注射 Aβ₄₂,原代培养神经元	[38]
ATB	↓	负性调节miR-200,增加Aβ聚积	细胞系	[39]

长链非编码RNA在阿尔茨海默病中的研究进展

Research progress on lncRNAs in Alzheimer’s disease

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