Abstract
MicroRNAs (miRNAs) represent the first and most prominent group of abundant small non-coding RNA molecules discovered to interfere with gene expression exclusively in eukaryotes. By targeting more than one mRNA each time through formation of miRNA:mRNA duplexes, miRNAs cause modulation of mRNA levels either through degradation or suppression of translation, thus affecting dynamic gene networks that control virtually all major cellular processes. Since their early discovery, miRNA expression profiles, deriving from a variety of biological samples have been recognized as sensitive markers or predictors of many clinical perturbations, including neurodegenerating diseases. A great number of either predicted or experimentally detectable and validated miRNAs is also present in the brain and has been implicated in neuron homeostasis and synaptic function. In addition, many studies associate deregulated miRNA expression with neurodegenerative diseases however, the dynamic gene networks that are affected by miRNA deregulation in connection to disease pathogenesis and progression, are still elusive to a great extent. The vast amount of data deriving from NGS-based transcriptomics analyses are available in various miRNA databases and facilitate the correlation of specific miRNAs with neurodegeneration. The ability of miRNAs to target multiple mRNAs and overall, more than 60% of gene expression in human, taken together with their ability to circulate in biological fluids, pinpoint their important role as nodal epigenetic regulators, and highlight their value as biomarkers for many neurodegenerative diseases. In this chapter, the emerging roles of miRNA deregulation in major neurodegenerative diseases and their progression is discussed.
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References
Abe M, Bonini NM (2013) MicroRNAs and neurodegeneration: role and impact. Trends Cell Biol 1:30–36. https://doi.org/10.1016/j.tcb.2012.08.013
Acharya S, Salgado-Somoza A, Stefanizzi FM, Lumley AI, Zhang L, Glaab E, May P, Devaux Y (2020) Non-coding RNAs in the brain-heart Axis: the case of Parkinson’s disease. Int J Mol Sci 21(18):6513. https://doi.org/10.3390/ijms21186513
Almeida MI, Reis RM, Calin GA (2011) MicroRNA history: discovery, recent applications, and next frontiers. Mutat Res 717(1–2):1–8. https://doi.org/10.1016/j.mrfmmm.2011.03.009
Angelucci F, Cechova K, Valis M, Kuca K, Zhang B, Hort J (2019) MicroRNAs in Alzheimer’s disease: diagnostic markers or therapeutic agents? Front Pharmacol 10:665. https://doi.org/10.3389/fphar.2019.00665
Arshad AR, Sulaiman SA, Saperi AA, Jamal R, Mohamed Ibrahim N, Abdul Murad NA (2017) MicroRNAs and target genes as biomarkers for the diagnosis of early onset of Parkinson disease. Front Mol Neurosci 10:352. https://doi.org/10.3389/fnmol.2017.00352
Bauer M, Kinkl N, Meixner A, Kremmer E, Riemenschneider M, Förstl H, Gasser T, Ueffing M (2009) Prevention of interferon-stimulated gene expression using microRNA-designed hairpins. Gene Ther 16(1):142–147. https://doi.org/10.1038/gt.2008.123
Beermann J, Piccoli MT, Viereck J, Thum T (2016) Non-coding RNAs in development and disease: background, mechanisms, and therapeutic approaches. Physiol Rev 96(4):1297–1325. https://doi.org/10.1152/physrev.00041.2015
Boese AS, Saba R, Campbell K, Majer A, Medina S, Burton L, Booth TF, Chong P, Westmacott G, Dutta SM, Saba JA, Booth SA (2016) MicroRNA abundance is altered in synaptoneurosomes during prion disease. Mol Cell Neurosci 71:13–24. https://doi.org/10.1016/j.mcn.2015.12.001
Catanesi M, d’Angelo M, Tupone MG, Benedetti E, Giordano A, Castelli V, Cimini A (2020) MicroRNAs dysregulation and mitochondrial dysfunction in neurodegenerative diseases. Int J Mol Sci 21(17):5986. https://doi.org/10.3390/ijms21175986
Chen TH (2020) Circulating microRNAs as potential biomarkers and therapeutic targets in spinal muscular atrophy. Ther Adv Neurol Disord 13:1756286420979954. https://doi.org/10.1177/1756286420979954
Chen TH, Chen JA (2019) Multifaceted roles of microRNAs: from motor neuron generation in embryos to degeneration in spinal muscular atrophy. elife 8:e50848. https://doi.org/10.7554/eLife.50848
Dardiotis E, Aloizou AM, Siokas V, Patrinos GP, Deretzi G, Mitsias P, Aschner M, Tsatsakis A (2018) The role of microRNAs in patients with amyotrophic lateral sclerosis. J Mol Neurosci 66(4):617–628. https://doi.org/10.1007/s12031-018-1204-1
Dong X, Cong S (2019) The emerging role of microRNAs in polyglutamine diseases. Front Mol Neurosci 12:156. https://doi.org/10.3389/fnmol.2019.00156
Dweep H, Sticht C, Pandey P, Gretz N (2011) miRWalk – database: prediction of possible miRNA binding sites by “walking” the genes of three genomes. J Biomed Inform 44(5):839–847. https://doi.org/10.1016/j.jbi.2011.05.002
Erson-Bensan AE (2014) Introduction to microRNAs in biological systems. Methods Mol Biol 1107:1–14. https://doi.org/10.1007/978-1-62703-748-8_1
Femminella GD, Ferrara N, Rengo G (2015) The emerging role of microRNAs in Alzheimer’s disease. Front Physiol 6:40. https://doi.org/10.3389/fphys.2015.00040
Fenoglio C, Ridolfi E, Galimberti D, Scarpini E (2012) MicroRNAs as active players in the pathogenesis of multiple sclerosis. Int J Mol Sci 10:13227–13239. https://doi.org/10.3390/ijms131013227
Fragkouli A, Doxakis E (2014) miR-7 and miR-153 protect neurons against MPP(+)-induced cell death via upregulation of mTOR pathway. Front Cell Neurosci 8:182. https://doi.org/10.3389/fncel.2014.00182
Goh SY, Chao YX, Dheen ST, Tan EK, Tay SS (2019) Role of microRNAs in Parkinson’s disease. Int J Mol Sci 20(22):5649. https://doi.org/10.3390/ijms20225649
Goodall EF, Heath PR, Bandmann O, Kirby J, Shaw PJ (2013) Neuronal dark matter: the emerging role of microRNAs in neurodegeneration. Front Cell Neurosci 7:178. https://doi.org/10.3389/fncel.2013.00178
Guerau-de-Arellano M, Smith KM, Godlewski J, Liu Y, Winger R, Lawler SE, Whitacre CC, Racke MK, Lovett-Racke AE (2011) Micro-RNA dysregulation in multiple sclerosis favours pro-inflammatory T-cell-mediated autoimmunity. Brain 134(Pt 12):3578–3589. https://doi.org/10.1093/brain/awr262
Hasler D, Lehmann G, Murakawa Y, Klironomos F, Jakob L, Grässer FA, Rajewsky N, Landthaler M, Meister G (2016) The lupus autoantigen La prevents mis-channeling of tRNA fragments into the human microRNA pathway. Mol Cell 63(1):110–124. https://doi.org/10.1016/j.molcel.2016.05.026
Hassani A, Khan G (2019) Epstein-Barr virus and miRNAs: partners in crime in the pathogenesis of multiple sclerosis? Front Immunol 10:695. https://doi.org/10.3389/fimmu.2019.00695
Huang Z, Shi J, Gao Y, Cui C, Zhang S, Li J, Zhou Y, Cui Q (2019) HMDD v3.0: a database for experimentally supported human microRNA-disease associations. Nucleic Acids Res 47(D1):D1013–D1017. https://doi.org/10.1093/nar/gky1010
Jiang Q, Wang Y, Hao Y, Juan L, Teng M, Zhang X, Li M, Wang G, Liu Y (2009) miR2Disease: a manually curated database for microRNA deregulation in human disease. Nucleic Acids Res 37(Database issue):D98–D104. https://doi.org/10.1093/nar/gkn714
Joilin G, Leigh PN, Newbury SF, Hafezparast M (2019) An overview of microRNAs as biomarkers of ALS. Front Neurol 10:186. https://doi.org/10.3389/fneur.2019.00186
Junker A, Krumbholz M, Eisele S, Mohan H, Augstein F, Bittner R, Lassmann H, Wekerle H, Hohlfeld R, Meinl E (2009) MicroRNA profiling of multiple sclerosis lesions identifies modulators of the regulatory protein CD47. Brain 132(Pt 12):3342–3352. https://doi.org/10.1093/brain/awp300
Juźwik CA, Drake S, Zhang Y, Paradis-Isler N, Sylvester A, Amar-Zifkin A, Douglas C, Morquette B, Moore CS, Fournier AE (2019) MicroRNA dysregulation in neurodegenerative diseases: a systematic review. Prog Neurobiol 182:101664. https://doi.org/10.1016/j.pneurobio.2019.101664
Koscianska E, Krzyzosiak WJ (2014) Current understanding of the role of microRNAs in spinocerebellar ataxias. Cerebellum Ataxias 1:7. https://doi.org/10.1186/2053-8871-1-7
Kozomara A, Birgaoanu M, Griffiths-Jones S (2019) miRbase: from microRNA sequences to function. Nucleic Acids Res 47(D1):D155–D162. https://doi.org/10.1093/nar/gky1141
Lee RC, Feinbaum RL, Ambros V (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75:843–854. https://doi.org/10.1016/0092-8674(93)90529-y
Leggio L, Vivarelli S, L’Episcopo F, Tirolo C, Caniglia S, Testa N, Marchetti B, Iraci N (2017) MicroRNAs in Parkinson’s disease: from pathogenesis to novel diagnostic and therapeutic approaches. Int J Mol Sci 18(12):2698. https://doi.org/10.3390/ijms18122698
Li J, Han X, Wan Y, Zhang S, Zhao Y, Fan R, Cui Q, Zhou Y (2018) TAM 2.0: tool for microRNA set analysis. Nucleic Acids Res 46(W1):W180–W185. https://doi.org/10.1093/nar/gky509
Liu CJ, Fu X, Xia M, Zhang Q, Gu Z, Guo AY (2021) miRNASNP-v3: a comprehensive database for SNPs and disease-related variations in miRNAs and miRNA targets. Nucleic Acids Res 49(D1):D1276–D1281. https://doi.org/10.1093/nar/gkaa783
Lukasik A, Wójcikowski M, Zielenkiewicz P (2016) Tools4miRs – one place to gather all the tools for miRNA analysis. Bioinformatics 32(17):2722–2724. https://doi.org/10.1093/bioinformatics/btw189
Maciotta S, Meregalli M, Torrente Y (2013) The involvement of microRNAs in neurodegenerative diseases. Front Cell Neurosci 7:265. https://doi.org/10.3389/fncel.2013.00265
Majer A, Medina SJ, Niu Y, Abrenica B, Manguiat KJ, Frost KL, Philipson CS, Sorensen DL, Booth SA (2012) Early mechanisms of pathobiology are revealed by transcriptional temporal dynamics in hippocampal CA1 neurons of prion infected mice. PLoS Pathog 8(11):e1003002. https://doi.org/10.1371/journal.ppat.1003002
Misiorek JO, Schreiber AM, Urbanek-Trzeciak MO, Jazurek-Ciesiołka M, Hauser LA, Lynch DR, Napierala JS, Napierala M (2020) A comprehensive transcriptome analysis identifies FXN and BDNF as novel targets of miRNAs in Friedreich’s ataxia patients. Mol Neurobiol 57(6):2639–2653. https://doi.org/10.1007/s12035-020-01899-1
Miya Shaik M, Tamargo IA, Abubakar MB, Kamal MA, Greig NH, Gan SH (2018) The role of microRNAs in Alzheimer’s disease and their therapeutic potentials. Genes (Basel) 9(4):174. https://doi.org/10.3390/genes9040174
Müller M, Fazi F, Ciaudo C (2020) Argonaute proteins: from structure to function in development and pathological cell fate determination. Front Cell Dev Biol 7:360. https://doi.org/10.3389/fcell.2019.00360
O’Brien J, Hayder H, Zayed Y, Peng C (2018) Overview of microRNA biogenesis, mechanisms of actions, and circulation. Front Endocrinol 9:402. https://doi.org/10.3389/fendo.2018.00402
Quinlan S, Kenny A, Medina M, Engel T, Jimenez-Mateos EM (2017) MicroRNAs in neurodegenerative diseases. Int Rev Cell Mol Biol 334:309–343. https://doi.org/10.1016/bs.ircmb.2017.04.002
Ruepp A, Kowarsch A, Schmidl D, Buggenthin F, Brauner B, Dunger I, Fobo G, Frishman G, Montrone C, Theis FJ (2010) PhenomiR: a knowledgebase for microRNA expression in diseases and biological processes. Genome Biol 11(1):R6. https://doi.org/10.1186/gb-2010-11-1-r6
Russo F, Di Bella S, Nigita G, Macca V, Laganà A, Giugno R, Pulvirenti A, Ferro A (2012) miRandola: extracellular circulating microRNAs database. PLoS One 7(10):e47786. https://doi.org/10.1371/journal.pone.0047786
Saba R, Goodman CD, Huzarewich RL, Robertson C, Booth SA (2008) A miRNA signature of prion induced neurodegeneration. PLoS One 3(11):e3652. https://doi.org/10.1371/journal.pone.0003652
Silvestro S, Bramanti P, Mazzon E (2019) Role of miRNAs in Alzheimer’s disease and possible fields of application. Int J Mol Sci 20(16):3979. https://doi.org/10.3390/ijms20163979
Truesdell SS, Mortensen RD, Seo M, Schroeder JC, Lee JH, LeTonqueze O, Vasudevan S (2012) MicroRNA-mediated mRNA translation activation in quiescent cells and oocytes involves recruitment of a nuclear microRNP. Sci Rep 2:842. https://doi.org/10.1038/srep00842
Ubhi K, Rockenstein E, Kragh C, Inglis C, Spencer B, Michael S, Mante M, Adame A, Galasko D, Masliah E (2014) Widespread microRNA dysregulation in multiple system atrophy – disease-related alteration in miR-96. Eur J Neurosci 39(6):1026–1041. https://doi.org/10.1111/ejn.12444
Viswambharan V, Thanseem I, Vasu MM, Poovathinal SA, Anitha A (2017) miRNAs as biomarkers of neurodegenerative disorders. Biomark Med 11(2):151–167. https://doi.org/10.2217/bmm-2016-0242
Wang L, Zhang L (2020) MicroRNAs in amyotrophic lateral sclerosis: from pathogenetic involvement to diagnostic biomarker and therapeutic agent development. Neurol Sci 12:3569–3577. https://doi.org/10.1007/s10072-020-04773-z
Wang M, Qin L, Tang B (2019) MicroRNAs in Alzheimer’s disease. Front Genet 10:153. https://doi.org/10.3389/fgene.2019.00153
Wightman B, Ha I, Ruvkun G (1993) Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell 75:855–862. https://doi.org/10.1016/0092-8674(93)90530-4
Xiang C, Han S, Nao J, Cong S (2019) MicroRNAs dysregulation and metabolism in multiple system atrophy. Front Neurosci 13:1103. https://doi.org/10.3389/fnins.2019.01103
Yang JX, Rastetter RH, Wilhelm D (2016) Non-coding RNAs: an introduction. Adv Exp Med Biol 886:13–32. https://doi.org/10.1007/978-94-017-7417-8_2
Yang X, Wu Y, Zhang B, Ni B (2018) Noncoding RNAs in multiple sclerosis. Clin Epigenetics 10(1):149. https://doi.org/10.1186/s13148-018-0586-9
Zare-Shahabadi A, Renaudineau Y, Rezaei N (2013) MicroRNAs and multiple sclerosis: from physiopathology toward therapy. Expert Opin Ther Targets 12:1497–1507. https://doi.org/10.1517/14728222.2013.838219
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Stathopoulos, C., Giarimoglou, N., Kouvela, A., Alexiou, A., Stamatopoulou, V. (2023). MicroRNAs in Neurodegenerative Diseases. In: Vlamos, P., Kotsireas, I.S., Tarnanas, I. (eds) Handbook of Computational Neurodegeneration. Springer, Cham. https://doi.org/10.1007/978-3-319-75922-7_49
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