长链非编码RNA在阿尔茨海默病中的研究进展

熊婉迪, 徐开宇, 陆林, 李家立

doi:10.16288/j.yczz.21-427

遗传 >

2022 , Vol. 44 >Issue 3: 189 - 197

DOI: https://doi.org/10.16288/j.yczz.21-427

综述

长链非编码RNA在阿尔茨海默病中的研究进展

展开

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;

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

收稿日期: 2021-12-20

修回日期: 2022-01-21

网络出版日期: 2022-02-16

基金资助

国家自然科学基金项目资助(81761128036)

收起

Research progress on lncRNAs in Alzheimer’s disease

Expand

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 date: 2021-12-20

Revised date: 2022-01-21

Online published: 2022-02-16

Supported by

Supported by the National Natural Science Foundation of China(81761128036)

Fold

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

本文引用格式

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 . DOI: 10.16288/j.yczz.21-427

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

参考文献

[1]	Brody H. Alzheimer's disease. Nature, 2011,475(7355):S1.
[2]	Hodson R. Alzheimer's disease. Nature, 2018,559(7715):S1.
[3]	Busche MA, Wegmann S, Dujardin S, Commins C, Schiantarelli J, Klickstein N, Kamath TV, Carlson GA, Nelken I, Hyman BT. Tau impairs neural circuits, dominating amyloid-β effects, in Alzheimer models in vivo. Nat Neurosci, 2019,22(1):57-64.
[4]	Quirion R, Wilson A, Rowe W, Aubert I, Richard J, Doods H, Parent A, White N, Meaney MJ. Facilitation of acetylcholine release and cognitive performance by an M(2)- muscarinic receptor antagonist in aged memory-impaired. J Neurosci, 1995,15(2):1455-1462.
[5]	Butterfield DA, Halliwell B. Oxidative stress, dysfunctional glucose metabolism and Alzheimer disease. Nat Rev Neurosci, 2019,20(3):148-160.
[6]	Kuehn BM. In Alzheimer research, glucose metabolism moves to center stage. JAMA, 2020,323(4):297-299.
[7]	Swerdlow RH. Mitochondria and mitochondrial cascades in Alzheimer's disease. J Alzheimers Dis, 2018,62(3):1403-1416.
[8]	Swerdlow RH, Burns JM, Khan SM. The Alzheimer's disease mitochondrial cascade hypothesis. J Alzheimers Dis, 2010, 20 Suppl 2(Suppl 2): S265-S279.
[9]	Xie CL, Zhuang XX, Niu ZM, Ai RX, Lautrup S, Zheng SJ, Jiang YH, Han RY, Gupta TS, Cao SQ, Lagartos- Donate MJ, Cai CZ, Xie LM, Caponio D, Wang WW, Schmauck-Medina T, Zhang JY, Wang HL, Lou GF, Xiao XL, Zheng WH, Palikaras K, Yang G, Caldwell KA, Caldwell GA, Shen HM, Nilsen H, Lu JH, Fang EF. Amelioration of Alzheimer's disease pathology by mitophagy inducers identified via machine learning and a cross-species workflow. Nat Biomed Eng, 2022,6(1):76-93.
[10]	Fyfe I. Single-cell atlas maps cell-specific gene changes in Alzheimer disease. Nat Rev Neurol, 2020,16(1):1.
[11]	Palazzo AF, Koonin EV. Functional long non-coding RNAs evolve from junk transcripts. Cell, 2020,183(5):1151-1161.
[12]	Yang F, Yi F, Cao HQ, Liang ZC, Du Q . The emerging landscape of long non-coding RNAs. Hereditas(Beijing), 2014,36(5):456-468.
[12]	杨峰, 易凡, 曹慧青, 梁子才, 杜权 . 长链非编码RNA研究进展. 遗传, 2014,36(5):456-468.
[13]	Sharma H, Carninci P. The secret life of lncRNAs: conserved, yet not conserved. Cell, 2020,181(3):512-514.
[14]	Engreitz JM, Haines JE, Perez EM, Munson G, Chen J, Kane M, McDonel PE, Guttman M, Lander ES,. Local regulation of gene expression by lncRNA promoters, transcription and splicing. Nature, 2016,539(7629):452-455.
[15]	Statello L, Guo CJ, Chen LL, Huarte M. Gene regulation by long non-coding RNAs and its biological functions. Nat Rev Mol Cell Biol, 2021,22(2):96-118.
[16]	Tang SS, Zheng BY, Xiong XD. LincRNA-p21: implications in human diseases. Int J Mol Sci, 2015,16(8):18732-18740.
[17]	Yoon JH, Abdelmohsen K, Srikantan S, Yang XL, Martindale JL, De S, Huarte M, Zhan M, Becker KG, Gorospe M. LincRNA-p21 suppresses target mRNA translation. Mol Cell, 2012,47(4):648-655.
[18]	de Silanes IL, Stagno d'Alcontres M, Blasco MA. TERRA transcripts are bound by a complex array of RNA-binding proteins. Nat Commun, 2010,1:33.
[19]	Aguado J, di Fagagna FD, Wolvetang E. Telomere transcription in ageing. Ageing Res Rev, 2020,62:101115.
[20]	Faghihi MA, Modarresi F, Khalil AM, Wood DE, Sahagan BG, Morgan TE, Finch CE, Laurent GS, Kenny PJ, Wahlestedt C. Expression of a noncoding RNA is elevated in Alzheimer's disease and drives rapid feed-forward regulation of beta-secretase. Nat Med, 2008,14(7):723-730.
[21]	Zeng T, Ni HT, Yu Y, Zhang MK, Wu MJ, Wang QL, Wang LJ, Xu S, Xu ZY, Xu C, Xiong J, Jiang JF, Luo Y, Wang Y, Liu HQ. BACE1-AS prevents BACE1 mRNA degradation through the sequestration of BACE1-targeting miRNAs. J Chem Neuroanat, 2019,98:87-96.
[22]	Rogaeva E, Meng Y, Lee JH, Gu YJ, Kawarai T, Zou FG, Katayama T, Baldwin CT, Cheng R, Hasegawa H, Chen FS, Shibata N, Lunetta KL, Pardossi-Piquard R, Bohm C, Wakutani Y, Cupples LA, Cuenco KT, Green RC, Pinessi L, Rainero I, Sorbi S, Bruni A, Duara R, Friedland RP, Inzelberg R, Hampe W, Bujo H, Song YQ, Andersen OM, Willnow TE, Graff-Radford N, Petersen RC, Dickson D, Der SD, Fraser PE, Schmitt-Ulms G, Younkin S, Mayeux R, Farrer LA, St George-Hyslop P. The neuronal sortilin- related receptor SORL1 is genetically associated with Alzheimer disease. Nat Genet, 2007,39(2):168-177.
[23]	Ciarlo E, Massone S, Penna I, Nizzari M, Gigoni A, Dieci G, Russo C, Florio T, Cancedda R, Pagano A. An intronic ncRNA-dependent regulation of SORL1 expression affecting Aβ formation is upregulated in post-mortem Alzheimer's disease brain samples. Dis Model Mech, 2013,6(2):424-433.
[24]	Mus E, Hof PR, Tiedge H. Dendritic BC200 RNA in aging and in Alzheimer's disease. Proc Natl Acad Sci USA, 2007,104(25):10679-10684.
[25]	Yang SM, Lim KH, Kim SH, Joo JY. Molecular landscape of long noncoding RNAs in brain disorders. Mol Psychiatry, 2021,26(4):1060-1074.
[26]	Li HY, Zheng L, Jiang AH, Mo Y, Gong Q. Identification of the biological affection of long noncoding RNA BC200 in Alzheimer's disease. Neuroreport, 2018,29(13):1061-1067.
[27]	Mori Y, Tsuji M, Oguchi T, Kasuga K, Kimura A, Futamura A, Sugimoto A, Kasai H, Kuroda T, Yano S, Hieda S, Kiuchi Y, Ikeuchi T, Ono K. Serum BDNF as a potential biomarker of Alzheimer's disease: verification through assessment of serum, cerebrospinal fluid, and medial temporal lobe atrophy. Front Neurol, 2021,12:653267.
[28]	Policarpo R, Sierksma A, De Strooper B, d'Ydewalle C,. From junk to function: lncRNAs in CNS health and disease. Front Mol Neurosci, 2021,14:714768.
[29]	Modarresi F, Faghihi MA, Lopez-Toledano MA, Fatemi RP, Magistri M, Brothers SP, van der Brug MP, Wahlestedt C,. Inhibition of natural antisense transcripts in vivo results in gene-specific transcriptional upregulation. Nat Biotechnol, 2012,30(5):453-459.
[30]	Ding YT, Luan WK, Shen XL, Wang Z, Cao YJ. LncRNA BDNF-AS as ceRNA regulates the miR-9-5p/BACE1 pathway affecting neurotoxicity in Alzheimer's disease. Arch Gerontol Geriatr, 2022,99:104614.
[31]	Massone S, Ciarlo E, Vella S, Nizzari M, Florio T, Russo C, Cancedda R, Pagano A. NDM29, a RNA polymerase III-dependent non coding RNA, promotes amyloidogenic processing of APP and amyloid β secretion. Biochim Biophys Acta, 2012,1823(7):1170-1177.
[32]	Ahmadi S, Zobeiri M, Bradburn S. Molecular mechanisms underlying actions of certain long noncoding RNAs in Alzheimer's disease. Metab Brain Dis, 2020,35(5):681-693.
[33]	Massone S, Vassallo I, Fiorino G, Castelnuovo M, Barbieri F, Borghi R, Tabaton M, Robello M, Gatta E, Russo C, Florio T, Dieci G, Cancedda R, Pagano A. 17A, a novel non-coding RNA, regulates GABA B alternative splicing and signaling in response to inflammatory stimuli and in Alzheimer disease. Neurobiol Dis, 2011,41(2):308-317.
[34]	Yin RH, Yu JT, Tan L. The role of SORL1 in Alzheimer's disease. Mol Neurobiol, 2015,51(3):909-918.
[35]	Chen FH, Danladi J, Ardalan M, Elfving B, Müller HK, Wegener G, Sanchez C, Nyengaard JR. A critical role of mitochondria in BDNF-associated synaptic plasticity after one-week vortioxetine treatment. Int J Neuropsychopharmacol, 2018,21(6):603-615.
[36]	Huang ZH, Zhao J, Wang W, Zhou J, Zhang J. Depletion of lncRNA NEAT1 rescues mitochondrial dysfunction through NEDD4L-dependent PINK1 degradation in animal models of Alzheimer's disease. Front Cell Neurosci, 2020,14:28.
[37]	Gu C, Chen C, Wu RP, Dong T, Hu XJ, Yao YP, Zhang Y. Long noncoding RNA EBF3-AS promotes neuron apoptosis in Alzheimer's disease. DNA Cell Biol, 2018,37(3):220-226.
[38]	Zhang L, Fang Y, Cheng X, Lian YJ, Xu HL. Silencing of long noncoding RNA SOX21-AS1 relieves neuronal oxidative stress injury in mice with Alzheimer's disease by upregulating FZD3/5 via the Wnt signaling pathway. Mol Neurobiol, 2019,56(5):3522-3537.
[39]	Wang JD, Zhou TT, Wang T, Wang BL. Suppression of lncRNA-ATB prevents amyloid-β-induced neurotoxicity in PC12 cells via regulating miR-200/ZNF217 axis. Biomed Pharmacother, 2018,108:707-715.
[40]	Mercer TR, Neph S, Dinger ME, Crawford J, Smith MA, Shearwood AM, Haugen E, Bracken CP, Rackham O, Stamatoyannopoulos JA, Filipovska A, Mattick JS. The human mitochondrial transcriptome. Cell, 2011,146(4):645-658.
[41]	Rackham O, Shearwood AMJ, Mercer TR, Davies SMK, Mattick JS, Filipovska A. Long noncoding RNAs are generated from the mitochondrial genome and regulated by nuclear-encoded proteins. RNA, 2011,17(12):2085-2093.
[42]	Liu SL, Wang ZB, Chen D, Zhang BW, Tian RR, Wu J, Zhang Y, Xu KY, Yang LM, Cheng C, Ma J, Lv LB, Zheng YT, Hu XT, Zhang Y, Wang XT, Li JL. Annotation and cluster analysis of spatiotemporal- and sex-related lncRNA expression in rhesus macaque brain. Genome Res, 2017,27(9):1608-1620.

Options

文章导航

〈

〉

www.chinagene.cn
备案号：京ICP备09063187号-4
总访问:,今日访问:,当前在线:

模态框（Modal）标题

摘要

本文引用格式

Abstract

参考文献