Skip to main content

RNA Modifications in Neurodegenerations

  • Chapter
  • First Online:
Epitranscriptomics

Abstract

Considerable evidence is accumulating about the regulatory function of coding- and non-coding RNAs through chemical modifications on their own nitrogen bases. The mechanisms by which the amount and types of these modifications are built to each type of RNA are yet poorly clarified, although some classes of proteins have been identified as actors able to introduce (writers), specifically recognize (readers) or delate (erasers) such modifications. In this context, advances have been made thanks to bioinformatic tools, which have allowed a comprehensive database, where RNA processing and post-transcriptional modification are integrated and elucidated, to be generated. Now, it is accepted that the abovementioned epitranscriptome interplay is involved in orchestrating development, health, and disease, also including the development, function, and dysfunction of the nervous system. In this chapter, we aim at reviewing and describing the potential mechanisms associated with the dysregulation of the epitranscriptome and neuropathologies, focusing specifically on brain cancer and neurodegenerative disorders.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Alvarez-Dominguez JR, Lodish HF (2017) Emerging mechanisms of long noncoding RNA function during normal and malignant hematopoiesis. Blood 130:1965–1975

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Alzheimer’s Association (2020) Alzheimer’s disease facts and figures. Alzheimers Dement. https://doi.org/10.1002/alz.12068

  • Amlie-Wolf A, Tang M, Way J et al (2019) Inferring the molecular mechanisms of noncoding Alzheimer’s disease-associated genetic variants. J Alzheimers Dis 72:301–318

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • An H, Williams NG, Shelkovnikova TA (2018) NEAT1 and paraspeckles in neurodegenerative diseases: A missing lnc found? Noncoding RNA Res 3:243–252

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Angelbello AJ, Chen JL, Disney MD (2020) Small molecule targeting of RNA structures in neurological disorders. Ann NY Acad Sci 1471:57–71

    Article  CAS  PubMed  Google Scholar 

  • Angelova MT, Dimitrova DG, Dinges N et al (2018) The emerging field of epitranscriptomics in neurodevelopmental and neuronal disorders. Front Bioeng Biotechnol 6:46

    Article  PubMed  PubMed Central  Google Scholar 

  • Arena A, Iyer AM, Milenkovic I et al (2017) Developmental expression and dysregulation of miR-146a and miR-155 in Down’s syndrome and mouse models of Down’s syndrome and Alzheimer’s disease. Curr Alzheimer Res 14:1305–1317

    Article  CAS  PubMed  Google Scholar 

  • Argentati C, Tortorella I, Bazzucchi M et al (2020) The other side of Alzheimer’s disease: influence of metabolic disorder features for novel diagnostic biomarkers. J Pers Med 10:115

    Article  PubMed Central  Google Scholar 

  • Armstrong RA (2019) Risk factors for Alzheimer’s disease. Folia Neuropathol 57:87–105

    Article  Google Scholar 

  • Asano K, Suzuki T, Saito A et al (2018) Metabolic and chemical regulation of tRNA modification associated with taurine deficiency and human disease. Nucleic Acids Res 46:1565–1583

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bagyinszky E, Giau VV, An SA (2020) Transcriptomics in Alzheimer’s disease: aspects and challenges. Int J Mol Sci 21. https://doi.org/10.3390/ijms21103517

  • Balestrino R, Schapira AHV (2020) Parkinson disease. Eur J Neurol 27:27–42

    Article  CAS  PubMed  Google Scholar 

  • Banelli B, Forlani A, Allemanni G et al (2017) MicroRNA in glioblastoma: an overview. Int J Genomics 2017:7639084

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Barbagallo D, Condorelli A, Ragusa M et al (2016) Dysregulated miR-671-5p / CDR1-AS / CDR1 / VSNL1 axis is involved in glioblastoma multiforme. Oncotarget 7:4746–4759

    Article  PubMed  Google Scholar 

  • Barbagallo D, Caponnetto A, Cirnigliaro M et al (2018) CircSMARCA5 inhibits migration of glioblastoma multiforme cells by regulating a molecular axis involving splicing factors SRSF1/SRSF3/PTB. Int J Mol Sci 19:480

    Article  PubMed Central  CAS  Google Scholar 

  • Barbieri I, Kouzarides T (2020) Role of RNA modifications in cancer. Nat Rev Cancer 20:303–322

    Article  CAS  PubMed  Google Scholar 

  • Bassi S, Tripathi T, Monziani A et al (2017) Epigenetics of Huntington’s disease. Adv Exp Med Biol 978:277–299

    Article  CAS  PubMed  Google Scholar 

  • Bennett SA, Tanaz R, Cobos SN et al (2019) Epigenetics in amyotrophic lateral sclerosis: a role for histone post-translational modifications in neurodegenerative disease. Transl Res 204:19–30

    Article  CAS  PubMed  Google Scholar 

  • Bertram L, Tanzi RE (2019) Alzheimer disease risk genes: 29 and counting. Nat Rev Neurol 15:191–192

    Article  PubMed  Google Scholar 

  • Biamonti G, Amato A, Belloni E et al (2019) Alternative splicing in Alzheimer’s disease. Aging Clin Exp Res. https://doi.org/10.1007/s40520-019-01360-x

  • Bicchi I, Morena F, Montesano S et al (2013) MicroRNAs and molecular mechanisms of neurodegeneration. Genes (Basel) 4:244–263

    Article  CAS  Google Scholar 

  • Boccaletto P, Machnicka MA, Purta E et al (2018) MODOMICS: a database of RNA modification pathways. 2017 update. Nucleic Acids Res 46:D303–D307

    Article  CAS  PubMed  Google Scholar 

  • Bogomazova AN, Eremeev AV, Pozmogova GE et al (2019) The role of mutant RNA in the pathogenesis of Huntington’s disease and other polyglutamine diseases. Mol Biol (Mosk) 53:954–967

    Article  CAS  Google Scholar 

  • Bohnsack MT, Sloan KE (2018) The mitochondrial epitranscriptome: the roles of RNA modifications in mitochondrial translation and human disease. Cell Mol Life Sci 75:241–260

    Article  CAS  PubMed  Google Scholar 

  • Botti V, Cesaretti A, Ban Ž et al (2019) Fine structural tuning of styryl-based dyes for fluorescence and CD-based sensing of various ds-DNA/RNA sequences. Org Biomol Chem 17:8243–8258

    Article  CAS  PubMed  Google Scholar 

  • Botti V, Urbanelli L, Sagini K et al (2020) Quaternized styryl-azinium fluorophores as cellular RNA-binders. Photochem Photobiol Sci 19:362–370

    Article  CAS  PubMed  Google Scholar 

  • Braggin JE, Bucks SA, Course MM et al (2019) Alternative splicing in a presenilin 2 variant associated with Alzheimer disease. Ann Clin Transl Neurol 6:762–777

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Briggs JA, Wolvetang EJ, Mattick JS et al (2015) Mechanisms of long non-coding RNAs in mammalian nervous system development, plasticity, disease, and evolution. Neuron 88:861–877

    Article  CAS  PubMed  Google Scholar 

  • Brodie S, Lee HK, Jiang W et al (2017) The novel long non-coding RNA TALNEC2, regulates tumor cell growth and the stemness and radiation response of glioma stem cells. Oncotarget 8:31785–31801

    Article  PubMed  PubMed Central  Google Scholar 

  • Bucha S, Mukhopadhyay D, Bhattacharyya NP (2015) Regulation of mitochondrial morphology and cell cycle by microRNA-214 targeting Mitofusin2. Biochem Biophys Res Commun 465:797–802

    Article  CAS  PubMed  Google Scholar 

  • Burk K, Pasterkamp RJ (2019) Disrupted neuronal trafficking in amyotrophic lateral sclerosis. Acta Neuropathol 137:859–877

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Butti Z, Patten SA (2018) RNA dysregulation in amyotrophic lateral sclerosis. Front Genet 9:712

    Article  CAS  PubMed  Google Scholar 

  • Cai H, Liu X, Zheng J et al (2017) Long non-coding RNA taurine upregulated 1 enhances tumor-induced angiogenesis through inhibiting microRNA-299 in human glioblastoma. Oncogene 36:318–331

    Article  CAS  PubMed  Google Scholar 

  • Calzoni E, Cesaretti A, Polchi A et al (2019) Biocompatible polymer nanoparticles for drug delivery applications in cancer and neurodegenerative disorder therapies. J Funct Biomater 10:4

    Article  CAS  PubMed Central  Google Scholar 

  • Campos-Melo D, Droppelmann CA, He Z et al (2013) Altered microRNA expression profile in amyotrophic lateral sclerosis: a role in the regulation of NFL mRNA levels. Mol Brain 6:26

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cao M, Li H, Zhao J et al (2019) Identification of age- and gender-associated long noncoding RNAs in the human brain with Alzheimer’s disease. Neurobiol Aging 81:116–126

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Catanesi M, d’Angelo M, Tupone MG et al (2020) MicroRNAs dysregulation and mitochondrial dysfunction in neurodegenerative diseases. Int J Mol Sci 21:5986

    Article  CAS  PubMed Central  Google Scholar 

  • Ceyzériat K, Zilli T, Millet P et al (2020) Learning from the past: a review of clinical trials targeting amyloid, tau and neuroinflammation in Alzheimer’s disease. Curr Alzheimer Res 17:112–125

    Article  PubMed  CAS  Google Scholar 

  • Chanda K, Das S, Chakraborty J et al (2018) Altered levels of long NcRNAs Meg3 and Neat1 in cell and animal models of Huntington’s disease. RNA Biol 15:1348–1363

    Article  PubMed  PubMed Central  Google Scholar 

  • Chen X-Q, Mobley WC (2019) Alzheimer disease pathogenesis: insights from molecular and cellular biology studies of oligomeric Aβ and Tau species. Front Neurosci 13:659

    Article  PubMed  PubMed Central  Google Scholar 

  • Chen G, Wang Z, Wang D et al (2013) LncRNADisease: a database for long-non-coding RNA-associated diseases. Nucleic Acids Res 41:D983–D986

    Article  CAS  PubMed  Google Scholar 

  • Chen Y, Lian Y-J, Ma Y-Q et al (2018) LncRNA SNHG1 promotes α-synuclein aggregation and toxicity by targeting miR-15b-5p to activate SIAH1 in human neuroblastoma SH-SY5Y cells. Neurotoxicology 68:212–221

    Article  CAS  PubMed  Google Scholar 

  • Chen F-Z, Zhao Y, Chen H-Z (2019a) MicroRNA-98 reduces amyloid β-protein production and improves oxidative stress and mitochondrial dysfunction through the Notch signaling pathway via HEY2 in Alzheimer’s disease mice. Int J Mol Med 43:91–102

    CAS  PubMed  Google Scholar 

  • Chen X, Yu C, Guo M et al (2019b) Down-regulation of m6A mRNA methylation is involved in dopaminergic neuronal death. ACS Chem Neurosci 10:2355–2363

    Article  CAS  PubMed  Google Scholar 

  • Cheng C, Spengler RM, Keiser MS et al (2018) The long non-coding RNA NEAT1 is elevated in polyglutamine repeat expansion diseases and protects from disease gene-dependent toxicities. Hum Mol Genet 27:4303–4314

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chia R, Chiò A, Traynor BJ (2018) Novel genes associated with amyotrophic lateral sclerosis: diagnostic and clinical implications. Lancet Neurol 17:94–102

    Article  CAS  PubMed  Google Scholar 

  • Cho HJ, Liu G, Jin SM et al (2013) MicroRNA-205 regulates the expression of Parkinson’s disease-related leucine-rich repeat kinase 2 protein. Hum Mol Genet 22:608–620

    Article  CAS  PubMed  Google Scholar 

  • Cui Q, Shi H, Ye P et al (2017) m6A RNA methylation regulates the self-renewal and tumorigenesis of glioblastoma stem cells. Cell Rep 18:2622–2634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dahariya S, Paddibhatla I, Kumar S et al (2019) Long non-coding RNA: classification, biogenesis and functions in blood cells. Mol Immunol 112:82–92

    Article  CAS  PubMed  Google Scholar 

  • Dai D, Wang H, Zhu L et al (2018) N6-methyladenosine links RNA metabolism to cancer progression. Cell Death Dis 9:124

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Das U, Wang L, Ganguly A et al (2016) Visualizing APP and BACE-1 approximation in neurons yields insight into the amyloidogenic pathway. Nat Neurosci 19:55–64

    Article  CAS  PubMed  Google Scholar 

  • Dash D, Mestre TA (2020) Therapeutic update on Huntington’s disease: symptomatic treatments and emerging disease-modifying therapies. Neurotherapeutics. https://doi.org/10.1007/s13311-020-00891-w

  • De Felice B, Manfellotto F, Fiorentino G et al (2018) Wide-ranging analysis of microRNA profiles in sporadic amyotrophic lateral sclerosis using next-generation sequencing. Front Genet 9:310

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Delaidelli A, Jan A, Herms J et al (2019) Translational control in brain pathologies: biological significance and therapeutic opportunities. Acta Neuropathol 137:535–555

    Article  CAS  PubMed  Google Scholar 

  • DeVos SL, Miller RL, Schoch KM et al (2017) Tau reduction prevents neuronal loss and reverses pathological tau deposition and seeding in mice with tauopathy. Sci Transl Med 9:eaag0481

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Dolinar A, Koritnik B, Glavač D et al (2019) Circular RNAs as potential blood biomarkers in amyotrophic lateral sclerosis. Mol Neurobiol 56:8052–8062

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dong Z, Cui H (2020) The emerging roles of RNA modifications in glioblastoma. Cancers (Basel) 12:736

    Article  CAS  Google Scholar 

  • Dorszewska J, Prendecki M, Oczkowska A et al (2016) Molecular basis of familial and sporadic Alzheimer’s disease. Curr Alzheimer Res 13:952–963

    Article  CAS  PubMed  Google Scholar 

  • Dube U, Del-Aguila JL, Li Z et al (2019) An atlas of cortical circular RNA expression in Alzheimer disease brains demonstrates clinical and pathological associations. Nat Neurosci 22:1903–1912

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dykes IM, Emanueli C (2017) Transcriptional and post-transcriptional gene regulation by long non-coding RNA. Genomics Proteomics Bioinformatics 15:177–186

    Article  PubMed  PubMed Central  Google Scholar 

  • Eom GH, Kim K-B, Kim JH et al (2011) Histone methyltransferase SETD3 regulates muscle differentiation. J Biol Chem 286:34733–34742

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Essack M, Salhi A, Van Neste C et al (2020) DES-ROD: exploring literature to develop new links between RNA oxidation and human diseases. Oxid Med Cell Longev 2020:5904315

    Article  PubMed  PubMed Central  Google Scholar 

  • Esteller M (2011) Non-coding RNAs in human disease. Nat Rev Genet 12:861–874

    Article  CAS  PubMed  Google Scholar 

  • Esteve-Puig R, Bueno-Costa A, Esteller M (2020) Writers, readers and erasers of RNA modifications in cancer. Cancer Lett 474:127–137

    Article  CAS  PubMed  Google Scholar 

  • Faghihi MA, Modarresi F, Khalil AM et al (2008) Expression of a noncoding RNA is elevated in Alzheimer’s disease and drives rapid feed-forward regulation of beta-secretase. Nat Med 14:723–730

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Faghihi MA, Zhang M, Huang J et al (2010) Evidence for natural antisense transcript-mediated inhibition of microRNA function. Genome Biol 11:R56

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Fan W, Liang C, Ou M et al (2020) MicroRNA-146a is a wide-reaching neuroinflammatory regulator and potential treatment target in neurological diseases. Front Mol Neurosci 13:90

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fang M, Wang J, Zhang X et al (2012) The miR-124 regulates the expression of BACE1/β-secretase correlated with cell death in Alzheimer’s disease. Toxicol Lett 209:94–105

    Article  CAS  PubMed  Google Scholar 

  • Farr SA, Ripley JL, Sultana R et al (2014) Antisense oligonucleotide against GSK-3β in brain of SAMP8 mice improves learning and memory and decreases oxidative stress: involvement of transcription factor Nrf2 and implications for Alzheimer disease. Free Radic Biol Med 67:387–395

    Article  CAS  PubMed  Google Scholar 

  • Fernandes JCR, Acuña SM, Aoki JI et al (2019) Long non-coding RNAs in the regulation of gene expression: physiology and disease. Noncoding RNA 5:17

    Article  CAS  PubMed Central  Google Scholar 

  • Ferrante M, Conti GO (2017) Environment and neurodegenerative diseases: an update on miRNA role. Microrna 6:157–165

    Article  CAS  PubMed  Google Scholar 

  • Fisher AJ, Beal PA (2018) Structural basis for eukaryotic mRNA modification. Curr Opin Struct Biol 53:59–68

    Article  CAS  PubMed  Google Scholar 

  • Flamand MN, Meyer KD (2019) The epitranscriptome and synaptic plasticity. Curr Opin Neurobiol 59:41–48

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fotuhi SN, Khalaj-Kondori M, Hoseinpour Feizi MA et al (2019) Long non-coding RNA BACE1-AS may serve as an Alzheimer’s disease blood-based biomarker. J Mol Neurosci 69:351–359

    Article  CAS  PubMed  Google Scholar 

  • Fransquet PD, Ryan J (2018) Micro RNA as a potential blood-based epigenetic biomarker for Alzheimer’s disease. Clin Biochem 58:5–14

    Article  CAS  PubMed  Google Scholar 

  • Fusilli C, Migliore S, Mazza T et al (2018) Biological and clinical manifestations of juvenile Huntington’s disease: a retrospective analysis. Lancet Neurol 17:986–993

    Article  PubMed  Google Scholar 

  • Gagliardi D, Dziembowski A (2018) 5’ and 3’ modifications controlling RNA degradation: from safeguards to executioners. Philos Trans R Soc Lond B Biol Sci 373:20180160

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Gagliardi S, Zucca S, Pandini C et al (2018) Long non-coding and coding RNAs characterization in peripheral blood mononuclear cells and spinal cord from amyotrophic lateral sclerosis patients. Sci Rep 8:2378

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Galardi S, Michienzi A, Ciafrè SA (2020) Insights into the regulatory role of m6A epitranscriptome in glioblastoma. Int J Mol Sci 21:2816

    Article  CAS  PubMed Central  Google Scholar 

  • Garcia HG, Berrocal A, Kim YJ et al (2020) Lighting up the central dogma for predictive developmental biology. Curr Top Dev Biol 137:1–35

    Article  CAS  PubMed  Google Scholar 

  • Garcia-Manteiga JM, D’Alessandro R, Meldolesi J (2019) News about the role of the transcription factor REST in neurons: from physiology to pathology. Int J Mol Sci 21:235

    Article  PubMed Central  CAS  Google Scholar 

  • Ge J, Yu Y-T (2013) RNA pseudouridylation: new insights into an old modification. Trends Biochem Sci 38:210–218

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ge B, Li S-L, Li F-R (2020) Astragaloside-IV regulates endoplasmic reticulum stress-mediated neuronal apoptosis in a murine model of Parkinson’s disease via the lincRNA-p21/CHOP pathway. Exp Mol Pathol 115:104478

    Article  CAS  PubMed  Google Scholar 

  • Geng L, Zhang T, Liu W et al (2018) Inhibition of miR-128 abates Aβ-mediated cytotoxicity by targeting PPAR-γ via NF-κB inactivation in primary mouse cortical neurons and Neuro2a cells. Yonsei Med J 59:1096–1106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ghosh A, Mizuno K, Tiwari SS et al (2020) Alzheimer’s disease-related dysregulation of mRNA translation causes key pathological features with ageing. Transl Psychiatry 10:192

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gillies GE, Pienaar IS, Vohra S et al (2014) Sex differences in Parkinson’s disease. Front Neuroendocrinol 35:370–384

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ginns EI, Mak SK-K, Ko N et al (2014) Neuroinflammation and α-synuclein accumulation in response to glucocerebrosidase deficiency are accompanied by synaptic dysfunction. Mol Genet Metab 111:152–162

    Article  CAS  PubMed  Google Scholar 

  • Gu C, Chen C, Wu R et al (2018) Long noncoding RNA EBF3-AS promotes neuron apoptosis in Alzheimer’s disease. DNA Cell Biol 37:220–226

    Article  CAS  PubMed  Google Scholar 

  • Guo R, Fan G, Zhang J et al (2017) A 9-microRNA signature in serum serves as a noninvasive biomarker in early diagnosis of Alzheimer’s disease. J Alzheimers Dis 60:1365–1377

    Article  CAS  PubMed  Google Scholar 

  • Guo T, Zhang D, Zeng Y et al (2020) Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease. Mol Neurodegener 15:40

    Article  PubMed  PubMed Central  Google Scholar 

  • Han S, Miller JE, Byun S et al (2019) Identification of exon skipping events associated with Alzheimer’s disease in the human hippocampus. BMC Med Genomics 12:13

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Han M, Liu Z, Xu Y et al (2020) Abnormality of m6A mRNA methylation is involved in Alzheimer’s disease. Front Neurosci 14:98

    Article  PubMed  PubMed Central  Google Scholar 

  • Hanan M, Simchovitz A, Yayon N et al (2020) A Parkinson’s disease CircRNAs resource reveals a link between circSLC8A1 and oxidative stress. EMBO Mol Med 12:e11942

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hartford CCR, Lal A (2020) When long noncoding becomes protein coding. Mol Cell Biol 40:e00528–e00519

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hébert SS, Horré K, Nicolaï L et al (2008) Loss of microRNA cluster miR-29a/b-1 in sporadic Alzheimer’s disease correlates with increased BACE1/beta-secretase expression. Proc Natl Acad Sci USA 105:6415–6420

    Article  PubMed  PubMed Central  Google Scholar 

  • Helm M, Motorin Y (2017) Detecting RNA modifications in the epitranscriptome: predict and validate. Nat Rev Genet 18:275–291

    Article  CAS  PubMed  Google Scholar 

  • Höglinger GU, Michel PP, Champy P et al (2005) Experimental evidence for a toxic etiology of tropical parkinsonism. Mov Disord 20:118–119

    Article  PubMed  Google Scholar 

  • Hon C-C, Ramilowski JA, Harshbarger J et al (2017) An atlas of human long non-coding RNAs with accurate 5’ ends. Nature 543:199–204

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hsu PJ, Shi H, He C (2017) Epitranscriptomic influences on development and disease. Genome Biol 18:197

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hu S, Wang H, Chen K et al (2015) MicroRNA-34c downregulation ameliorates amyloid-β-induced synaptic failure and memory deficits by targeting VAMP2. J Alzheimers Dis 48:673–686

    Article  CAS  PubMed  Google Scholar 

  • Huang T, Chen W, Liu J et al (2019a) Genome-wide identification of mRNA 5-methylcytosine in mammals. Nat Struct Mol Biol 26:380–388

    Article  CAS  PubMed  Google Scholar 

  • Huang Z, Shi J, Gao Y et al (2019b) HMDD v3.0: a database for experimentally supported human microRNA-disease associations. Nucleic Acids Res 47:D1013–D1017

    Article  CAS  PubMed  Google Scholar 

  • Huang AZ, Delaidelli A, Sorensen PH (2020a) RNA modifications in brain tumorigenesis. Acta Neuropathol Commun 8:64

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang H, Camats-Perna J, Medeiros R et al (2020b) Altered expression of the m6A methyltransferase METTL3 in Alzheimer’s disease. eNeuro 7:ENEURO.0125-20.2020

    Google Scholar 

  • Jacob R, Zander S, Gutschner T (2017) The dark side of the epitranscriptome: chemical modifications in long non-coding RNAs. Int J Mol Sci 18:2387

    Article  PubMed Central  CAS  Google Scholar 

  • Jain G, Stuendl A, Rao P et al (2019) A combined miRNA-piRNA signature to detect Alzheimer’s disease. Transl Psychiatry 9:250

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Jakubauskienė E, Vilys L, Pečiulienė I et al (2020) The role of hypoxia on Alzheimer’s disease-related APP and Tau mRNA formation. Gene 766:145146

    Article  PubMed  CAS  Google Scholar 

  • Janin M, Ortiz-Barahona V, de Moura MC et al (2019) Epigenetic loss of RNA-methyltransferase NSUN5 in glioma targets ribosomes to drive a stress adaptive translational program. Acta Neuropathol 138:1053–1074

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jiang Q, Shan K, Qun-Wang X et al (2016a) Long non-coding RNA-MIAT promotes neurovascular remodeling in the eye and brain. Oncotarget 7:49688–49698

    Article  PubMed  PubMed Central  Google Scholar 

  • Jiang X, Yan Y, Hu M et al (2016b) Increased level of H19 long noncoding RNA promotes invasion, angiogenesis, and stemness of glioblastoma cells. J Neurosurg 124:129–136

    Article  CAS  PubMed  Google Scholar 

  • Jin Y, Tu Q, Liu M (2018) MicroRNA-125b regulates Alzheimer’s disease through SphK1 regulation. Mol Med Rep 18:2373–2380

    CAS  PubMed  Google Scholar 

  • John A, Kubosumi A, Reddy PH (2020) Mitochondrial microRNAs in aging and neurodegenerative diseases. Cells 9:1345

    Article  CAS  PubMed Central  Google Scholar 

  • Jonkhout N, Tran J, Smith MA et al (2017) The RNA modification landscape in human disease. RNA 23:1754–1769

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jovicic A, Zaldivar Jolissaint JF, Moser R et al (2013) MicroRNA-22 (miR-22) overexpression is neuroprotective via general anti-apoptotic effects and may also target specific Huntington’s disease-related mechanisms. PLoS One 8:e54222

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jung Y, Goldman D (2018) Role of RNA modifications in brain and behavior. Genes Brain Behav 17:e12444

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Juźwik CA, Drake S, Zhang Y et al (2019) microRNA dysregulation in neurodegenerative diseases: a systematic review. Prog Neurobiol 182:101664

    Article  PubMed  CAS  Google Scholar 

  • Kawarada L, Suzuki T, Ohira T et al (2017) ALKBH1 is an RNA dioxygenase responsible for cytoplasmic and mitochondrial tRNA modifications. Nucleic Acids Res 45:7401–7415

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kenny A, Jiménez-Mateos EM, Zea-Sevilla MA et al (2019) Proteins and microRNAs are differentially expressed in tear fluid from patients with Alzheimer’s disease. Sci Rep 9:15437

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kilchert C, Sträßer K, Kunetsky V et al (2020) From parts lists to functional significance-RNA-protein interactions in gene regulation. Wiley Interdiscip Rev RNA 11:e1582

    Article  CAS  PubMed  Google Scholar 

  • Kim W, Lee Y, McKenna ND et al (2014) miR-126 contributes to Parkinson’s disease by dysregulating the insulin-like growth factor/phosphoinositide 3-kinase signaling. Neurobiol Aging 35:1712–1721

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kirchner S, Ignatova Z (2015) Emerging roles of tRNA in adaptive translation, signalling dynamics and disease. Nat Rev Genet 16:98–112

    Article  CAS  PubMed  Google Scholar 

  • Kong Y, Wu J, Zhang D et al (2015) The role of miR-124 in drosophila Alzheimer’s disease model by targeting delta in notch signaling pathway. Curr Mol Med 15:980–989

    Article  CAS  PubMed  Google Scholar 

  • Kong B, Wu P-C, Chen L et al (2016) microRNA-7 protects against 1-methyl-4-phenylpyridinium iodide-induced cell apoptosis in SH-SY5Y cells by directly targeting Krüpple-like factor 4. DNA Cell Biol 35:217–225

    Article  CAS  PubMed  Google Scholar 

  • Kraus TFJ, Haider M, Spanner J et al (2017) Altered long noncoding RNA expression precedes the course of Parkinson’s disease-a preliminary report. Mol Neurobiol 54:2869–2877

    Article  CAS  PubMed  Google Scholar 

  • Kumar A, Kumar V, Singh K et al (2020) Therapeutic advances for Huntington’s disease. Brain Sci 10:43

    Article  CAS  PubMed Central  Google Scholar 

  • Lafontaine DLJ (2015) Noncoding RNAs in eukaryotic ribosome biogenesis and function. Nat Struct Mol Biol 22:11–19

    Article  CAS  PubMed  Google Scholar 

  • Lant JT, Berg MD, Heinemann IU et al (2019) Pathways to disease from natural variations in human cytoplasmic tRNAs. J Biol Chem 294:5294–5308

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Le Gras S, Keime C, Anthony A et al (2017) Altered enhancer transcription underlies Huntington’s disease striatal transcriptional signature. Sci Rep 7:42875

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lee A, Gilbert RM (2016) Epidemiology of Parkinson disease. Neurol Clin 34:955–965

    Article  PubMed  Google Scholar 

  • Leidinger P, Backes C, Deutscher S et al (2013) A blood based 12-miRNA signature of Alzheimer disease patients. Genome Biol 14:R78

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Leighton LJ, Bredy TW (2018) Functional interplay between small non-coding RNAs and RNA modification in the brain. Noncoding RNA 4:15

    Article  PubMed Central  Google Scholar 

  • Lentini JM, Ramos J, Fu D (2018) Monitoring the 5-methoxycarbonylmethyl-2-thiouridine (mcm5s2U) modification in eukaryotic tRNAs via the γ-toxin endonuclease. RNA 24:749–758

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lewis CJT, Pan T, Kalsotra A (2017) RNA modifications and structures cooperate to guide RNA-protein interactions. Nat Rev Mol Cell Biol 18:202–210

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li J, Liu C (2019) Coding or noncoding, the converging concepts of RNAs. Front Genet 10:496

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li S, Lv X, Zhai K et al (2016) MicroRNA-7 inhibits neuronal apoptosis in a cellular Parkinson’s disease model by targeting Bax and Sirt2. Am J Transl Res 8:993–1004

    CAS  PubMed  PubMed Central  Google Scholar 

  • Li L, Liu H, Song H et al (2017) Let-7d microRNA attenuates 6-OHDA-induced injury by targeting caspase-3 in MN9D cells. J Mol Neurosci 63:403–411

    Article  CAS  PubMed  Google Scholar 

  • Li D, Yang H, Ma J et al (2018a) MicroRNA-30e regulates neuroinflammation in MPTP model of Parkinson’s disease by targeting Nlrp3. Hum Cell 31:106–115

    Article  PubMed  Google Scholar 

  • Li H, Ren Y, Mao K et al (2018b) FTO is involved in Alzheimer’s disease by targeting TSC1-mTOR-Tau signaling. Biochem Biophys Res Commun 498:234–239

    Article  CAS  PubMed  Google Scholar 

  • Li L, Xu J, Wu M et al (2018c) Protective role of microRNA-221 in Parkinson’s disease. Bratisl Lek Listy 119:22–27

    CAS  PubMed  Google Scholar 

  • Li J, Chen W, Yi Y et al (2019) miR-219-5p inhibits tau phosphorylation by targeting TTBK1 and GSK-3β in Alzheimer’s disease. J Cell Biochem 120:9936–9946

    Article  CAS  PubMed  Google Scholar 

  • Li D, Zhang J, Li X et al (2020a) Insights into lncRNAs in Alzheimer’s disease mechanisms. RNA Biol 1–11

    Google Scholar 

  • Li Y, Fan H, Sun J et al (2020b) Circular RNA expression profile of Alzheimer’s disease and its clinical significance as biomarkers for the disease risk and progression. Int J Biochem Cell Biol 123:105747

    Article  CAS  PubMed  Google Scholar 

  • Liguori M, Nuzziello N, Introna A et al (2018) Dysregulation of microRNAs and target genes networks in peripheral blood of patients with sporadic amyotrophic lateral sclerosis. Front Mol Neurosci 11:288

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Liu Y, Lu Z (2018) Long non-coding RNA NEAT1 mediates the toxic of Parkinson’s disease induced by MPTP/MPP+ via regulation of gene expression. Clin Exp Pharmacol Physiol 45:841–848

    Article  CAS  PubMed  Google Scholar 

  • Liu Z, Wang C, Wang X, Xu S (2015) Therapeutic effects of transplantation of As-MiR-937-expressing mesenchymal stem cells in murine model of Alzheimer’s disease. Cell Physiol Biochem 37:321–330

    Article  PubMed  CAS  Google Scholar 

  • Liu S, Cui B, Dai Z et al (2016) Long non-coding RNA HOTAIR promotes Parkinson’s disease induced by MPTP through up-regulating the expression of LRRK2. Curr Neurovasc Res 13:115–120

    Article  CAS  PubMed  Google Scholar 

  • Liu D, Tang H, Li X-Y et al (2017a) Targeting the HDAC2/HNF-4A/miR-101b/AMPK pathway rescues tauopathy and dendritic abnormalities in Alzheimer’s disease. Mol Ther 25:752–764

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu W, Zhang Q, Zhang J et al (2017b) Long non-coding RNA MALAT1 contributes to cell apoptosis by sponging miR-124 in Parkinson disease. Cell Biosci 7:19

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Liu H, Xu Y, Yao B et al (2020a) A novel N6-methyladenosine (m6A)-dependent fate decision for the lncRNA THOR. Cell Death Dis 11:613

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu L, Wang Y, Wu J et al (2020b) N6-methyladenosine: a potential breakthrough for human cancer. Mol Ther Nucleic Acids 19:804–813

    Article  CAS  PubMed  Google Scholar 

  • Liu Z, Chen X, Li Z et al (2020c) Role of RNA oxidation in neurodegenerative diseases. Int J Mol Sci 21:5022

    Article  CAS  PubMed Central  Google Scholar 

  • Livneh I, Moshitch-Moshkovitz S, Amariglio N et al (2020) The m6A epitranscriptome: transcriptome plasticity in brain development and function. Nat Rev Neurosci 21:36–51

    Article  CAS  PubMed  Google Scholar 

  • Lockhart J, Canfield J, Mong EF et al (2019) Nucleotide modification alters microRNA-dependent silencing of microRNA switches. Mol Ther Nucleic Acids 14:339–350

    Article  CAS  PubMed  Google Scholar 

  • Long JM, Holtzman DM (2019) Alzheimer disease: an update on pathobiology and treatment strategies. Cell 179:312–339

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Long JM, Ray B, Lahiri DK (2014) MicroRNA-339-5p down-regulates protein expression of β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) in human primary brain cultures and is reduced in brain tissue specimens of Alzheimer disease subjects. J Biol Chem 289:5184–5198

    Article  CAS  PubMed  Google Scholar 

  • Long JM, Maloney B, Rogers JT et al (2019) Novel upregulation of amyloid-β precursor protein (APP) by microRNA-346 via targeting of APP mRNA 5’-untranslated region: implications in Alzheimer’s disease. Mol Psychiat 24:345–363

    Article  CAS  Google Scholar 

  • Lontay B, Kiss A, Virág L et al (2020) How do post-translational modifications influence the pathomechanistic landscape of Huntington’s disease? A comprehensive review. Int J Mol Sci 21:4282

    Article  CAS  PubMed Central  Google Scholar 

  • Lukiw WJ, Zhao Y, Cui JG (2008) An NF-kappaB-sensitive micro RNA-146a-mediated inflammatory circuit in Alzheimer disease and in stressed human brain cells. J Biol Chem 283:31315–31322

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Magini A, Polchi A, Tozzi A et al (2015) Abnormal cortical lysosomal β-hexosaminidase and β-galactosidase activity at post-synaptic sites during Alzheimer’s disease progression. Int J Biochem Cell Biol 58:62–70

    Article  CAS  PubMed  Google Scholar 

  • Marsh J, Alifragis P (2018) Synaptic dysfunction in Alzheimer’s disease: the effects of amyloid beta on synaptic vesicle dynamics as a novel target for therapeutic intervention. Neural Regen Res 13:616–623

    Article  PubMed  PubMed Central  Google Scholar 

  • Martino S (2015) Therapy for lysosomal storage disorders: a matter for stem cells. Int J Stem Cell Res Transplant 3:1–2

    Google Scholar 

  • Martino S, Morena F, Barola C et al (2014) Proteomics and epigenetic mechanisms in stem cells. Current Proteomics 11:193–209

    Article  CAS  Google Scholar 

  • Mathis S, Goizet C, Soulages A et al (2019) Genetics of amyotrophic lateral sclerosis: a review. J Neurol Sci 399:217–226

    Article  CAS  PubMed  Google Scholar 

  • Meng S, Zhou H, Feng Z et al (2019) Epigenetics in neurodevelopment: emerging role of circular RNA. Front Cell Neurosci 13:327

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Migliore S, Jankovic J, Squitieri F (2019) Genetic counseling in Huntington’s disease: potential new challenges on horizon? Front Neurol 10:453

    Article  PubMed  PubMed Central  Google Scholar 

  • Millan MJ (2017) Linking deregulation of non-coding RNA to the core pathophysiology of Alzheimer’s disease: an integrative review. Prog Neurobiol 156:1–68

    Article  CAS  PubMed  Google Scholar 

  • Modi PK, Jaiswal S, Sharma P (2016) Regulation of neuronal cell cycle and apoptosis by microRNA 34a. Mol Cell Biol 36:84–94

    Article  CAS  PubMed  Google Scholar 

  • Mongelli A, Atlante S, Bachetti T et al (2020) Epigenetic signaling and RNA regulation in cardiovascular diseases. Int J Mol Sci 21:509

    Article  CAS  PubMed Central  Google Scholar 

  • Morena F, Argentati C, Trotta R et al (2017) A comparison of lysosomal enzymes expression levels in peripheral blood of mild- and severe-Alzheimer’s disease and MCI patients: implications for regenerative medicine approaches. Int J Mol Sci 18:1806

    Article  PubMed Central  CAS  Google Scholar 

  • Morena F, Argentati C, Bazzucchi M et al (2018) Above the epitranscriptome: RNA modifications and stem cell identity. Genes (Basel) 9:329

    Article  CAS  Google Scholar 

  • Morena F, Oikonomou V, Argentati C et al (2019) Integrated computational analysis highlights unique miRNA signatures in the subventricular zone and striatum of GM2 gangliosidosis animal models. Int J Mol Sci 20:3179

    Article  CAS  PubMed Central  Google Scholar 

  • Morena F, Argentati C, Acquati S et al (2020) Toward reference intervals of ARSA activity in the cerebrospinal fluid: implication for the clinical practice of metachromatic leukodystrophy. J Appl Lab Med. https://doi.org/10.1093/jalm/jfaa108

  • Nalls MA, Blauwendraat C, Vallerga CL et al (2019) Identification of novel risk loci, causal insights, and heritable risk for Parkinson’s disease: a meta-analysis of genome-wide association studies. Lancet Neurol 18:1091–1102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nan Y, Han L, Zhang A et al (2010) MiRNA-451 plays a role as tumor suppressor in human glioma cells. Brain Res 1359:14–21

    Article  CAS  PubMed  Google Scholar 

  • Neueder A (2019) RNA-mediated disease mechanisms in neurodegenerative disorders. J Mol Biol 431:1780–1791

    Article  CAS  PubMed  Google Scholar 

  • Neueder A, Bates GP (2018) RNA related pathology in Huntington’s disease. Adv Exp Med Biol 1049:85–101

    Article  CAS  PubMed  Google Scholar 

  • Nishimoto Y, Nakagawa S, Hirose T et al (2013) The long non-coding RNA nuclear-enriched abundant transcript 1_2 induces paraspeckle formation in the motor neuron during the early phase of amyotrophic lateral sclerosis. Mol Brain 6:31

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nourse J, Spada S, Danckwardt S (2020) Emerging roles of RNA 3’-end cleavage and polyadenylation in pathogenesis, diagnosis and therapy of human disorders. Biomolecules 10:915

    Article  CAS  PubMed Central  Google Scholar 

  • Noyce AJ, Bestwick JP, Silveira-Moriyama L et al (2012) Meta-analysis of early nonmotor features and risk factors for Parkinson disease. Ann Neurol 72:893–901

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Oerum S, Dégut C, Barraud P et al (2017) m1A post-transcriptional modification in tRNAs. Biomolecules 7:20

    Article  PubMed Central  CAS  Google Scholar 

  • Orlacchio A, Bernardi G, Orlacchio A et al (2007) RNA interference as a tool for Alzheimer’s disease therapy. Mini Rev Med Chem 7:1166–1176

    Article  CAS  PubMed  Google Scholar 

  • Orlacchio A, Bernardi G, Orlacchio A et al (2008) Patented therapeutic RNAi strategies for neurodegenerative diseases of the CNS. Exp Opin Therap Patents 18:1161–1174

    Article  CAS  Google Scholar 

  • Orozco-Díaz R, Sánchez-Álvarez A, Hernández-Hernández JM et al (2019) The interaction between RE1-silencing transcription factor (REST) and heat shock protein 90 as new therapeutic target against Huntington’s disease. PLoS One 14:e0220393

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Oskarsson B, Gendron TF, Staff NP (2018) Amyotrophic lateral sclerosis: an update for 2018. Mayo Clin Proc 93:1617–1628

    Article  PubMed  Google Scholar 

  • Ozsait B, Komurcu-Bayrak E, Levula M et al (2010) Niemann-Pick type C fibroblasts have a distinct microRNA profile related to lipid metabolism and certain cellular components. Biochem Biophys Res Commun 403:316–321

    Article  CAS  PubMed  Google Scholar 

  • Pan T (2018) Modifications and functional genomics of human transfer RNA. Cell Res 28:395–404

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Parisi C, Napoli G, Amadio S et al (2016) MicroRNA-125b regulates microglia activation and motor neuron death in ALS. Cell Death Differ 23:531–541

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Penke B, Szűcs M, Bogár F (2020) Oligomerization and conformational change turn monomeric β-amyloid and tau proteins toxic: their role in Alzheimer’s pathogenesis. Molecules 25:1659

    Article  CAS  PubMed Central  Google Scholar 

  • Platt FM, Boland B, van der Spoel AC (2012) The cell biology of disease: lysosomal storage disorders: the cellular impact of lysosomal dysfunction. J Cell Biol 199:723–734

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Postuma RB, Berg D, Stern M et al (2015) MDS clinical diagnostic criteria for Parkinson’s disease. Mov Disord 30:1591–1601

    Article  PubMed  Google Scholar 

  • Qin L, Min S, Shu L et al (2020) Genetic analysis of N6-methyladenosine modification genes in Parkinson’s disease. Neurobiol Aging 93:143.e9–143.e13

    Article  CAS  Google Scholar 

  • Quan Z, Zheng D, Qing H (2017) Regulatory roles of long non-coding RNAs in the central nervous system and associated neurodegenerative diseases. Front Cell Neurosci 11:175

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Queiroz MT, Pereira VG, do Nascimento CC et al (2016) The underexploited role of non-coding RNAs in lysosomal storage diseases. Front Endocrinol (Lausanne) 7:133

    Article  Google Scholar 

  • Quinlan S, Kenny A, Medina M et al (2017) MicroRNAs in neurodegenerative diseases. Int Rev Cell Mol Biol 334:309–343

    Article  CAS  PubMed  Google Scholar 

  • Quintavalle C, Garofalo M, Zanca C et al (2012) miR-221/222 overexpession in human glioblastoma increases invasiveness by targeting the protein phosphate PTPμ. Oncogene 31:858–868

    Article  CAS  PubMed  Google Scholar 

  • Rafels-Ybern À, Torres AG, Grau-Bove X et al (2018) Codon adaptation to tRNAs with Inosine modification at position 34 is widespread among eukaryotes and present in two bacterial phyla. RNA Biol 15:500–507

    Article  PubMed  Google Scholar 

  • Ravnik-Glavač M, Glavač D (2020) Circulating RNAs as potential biomarkers in amyotrophic lateral sclerosis. Int J Mol Sci 21:1714

    Article  PubMed Central  CAS  Google Scholar 

  • Ren J, Yang Y, Xue J et al (2018) Long noncoding RNA SNHG7 promotes the progression and growth of glioblastoma via inhibition of miR-5095. Biochem Biophys Res Commun 496:712–718

    Article  CAS  PubMed  Google Scholar 

  • Rinchetti P, Rizzuti M, Faravelli I et al (2018) MicroRNA metabolism and dysregulation in amyotrophic lateral sclerosis. Mol Neurobiol 55:2617–2630

    Article  CAS  PubMed  Google Scholar 

  • Riva P, Ratti A, Venturin M (2016) The long non-coding RNAs in neurodegenerative diseases: novel mechanisms of pathogenesis. Curr Alzheimer Res 13:1219–1231

    Article  CAS  PubMed  Google Scholar 

  • Rodriguez CM, Todd PK (2019) New pathologic mechanisms in nucleotide repeat expansion disorders. Neurobiol Dis 130:104515

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Romano G, Veneziano D, Nigita G et al (2018) RNA methylation in ncRNA: classes, detection, and molecular associations. Front Genet 9:243

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Romo L, Ashar-Patel A, Pfister E et al (2017) Alterations in mRNA 3’ UTR isoform abundance accompany gene expression changes in human Huntington’s disease brains. Cell Rep 20:3057–3070

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rong D, Sun H, Li Z et al (2017) An emerging function of circRNA-miRNAs-mRNA axis in human diseases. Oncotarget 8:73271–73281

    Article  PubMed  PubMed Central  Google Scholar 

  • Roundtree IA, Evans ME, Pan T et al (2017) Dynamic RNA modifications in gene expression regulation. Cell 169:1187–1200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rudich P, Watkins S, Lamitina T (2020) PolyQ-independent toxicity associated with novel translational products from CAG repeat expansions. PLoS One 15:e0227464

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Salvatori B, Biscarini S, Morlando M (2020) Non-coding RNAs in nervous system development and disease. Front Cell Dev Biol 8:273

    Article  PubMed  PubMed Central  Google Scholar 

  • Santa-Maria I, Alaniz ME, Renwick N et al (2015) Dysregulation of microRNA-219 promotes neurodegeneration through post-transcriptional regulation of tau. J Clin Invest 125:681–686

    Article  PubMed  PubMed Central  Google Scholar 

  • Sarkar S, Jun S, Rellick S et al (2016) Expression of microRNA-34a in Alzheimer’s disease brain targets genes linked to synaptic plasticity, energy metabolism, and resting state network activity. Brain Res 1646:139–151

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Saudou F, Humbert S (2016) The biology of huntingtin. Neuron 89:910–926

    Article  CAS  PubMed  Google Scholar 

  • Schymick JC, Scholz SW, Fung H-C et al (2007) Genome-wide genotyping in amyotrophic lateral sclerosis and neurologically normal controls: first stage analysis and public release of data. Lancet Neurol 6:322–328

    Article  CAS  PubMed  Google Scholar 

  • Scoles DR, Minikel EV, Pulst SM (2019) Antisense oligonucleotides: a primer. Neurol Genet 5:e323

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Selkoe DJ, Hardy J (2016) The amyloid hypothesis of Alzheimer’s disease at 25 years. EMBO Mol Med 8:595–608

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sergiev PV, Aleksashin NA, Chugunova AA et al (2018) Structural and evolutionary insights into ribosomal RNA methylation. Nat Chem Biol 14:226–235

    Article  CAS  PubMed  Google Scholar 

  • Shafik A, Schumann U, Evers M et al (2016) The emerging epitranscriptomics of long noncoding RNAs. Biochim Biophys Acta 1859:59–70

    Article  CAS  PubMed  Google Scholar 

  • Shannon KM (2020) Recent advances in the treatment of Huntington’s disease: targeting DNA and RNA. CNS Drugs 34:219–228

    Article  CAS  PubMed  Google Scholar 

  • Shao W, Peng D, Wang X (2017) Genetics of Alzheimer’s disease: from pathogenesis to clinical usage. J Clin Neurosci 45:1–8

    Article  CAS  PubMed  Google Scholar 

  • Shen J, Hodges TR, Song R et al (2018) Serum HOTAIR and GAS5 levels as predictors of survival in patients with glioblastoma. Mol Carcinog 57:137–141

    Article  CAS  PubMed  Google Scholar 

  • Shi J, Wang Y-J, Sun C-R et al (2017) Long noncoding RNA lncHERG promotes cell proliferation, migration and invasion in glioblastoma. Oncotarget 8:108031–108041

    Article  PubMed  PubMed Central  Google Scholar 

  • Shu M, Zheng X, Wu S et al (2011) Targeting oncogenic miR-335 inhibits growth and invasion of malignant astrocytoma cells. Mol Cancer 10:59

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sierksma A, Lu A, Salta E et al (2018) Deregulation of neuronal miRNAs induced by amyloid-β or TAU pathology. Mol Neurodegener 13:54

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sinha M, Ghose J, Bhattarcharyya NP (2011) Micro RNA -214,-150,-146a and-125b target huntingtin gene. RNA Biol 8:1005–1021

    Article  CAS  PubMed  Google Scholar 

  • Smith AV, Tabrizi SJ (2020) Therapeutic antisense targeting of huntingtin. DNA Cell Biol 39:154–158

    Article  CAS  PubMed  Google Scholar 

  • Smith PY, Hernandez-Rapp J, Jolivette F et al (2015) miR-132/212 deficiency impairs tau metabolism and promotes pathological aggregation in vivo. Hum Mol Genet 24:6721–6735

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Song J, Yi C (2019) Reading chemical modifications in the transcriptome. J Mol Biol. S0022-2836(19):30598–30594

    Google Scholar 

  • Sun W, Samimi H, Gamez M et al (2018) Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies. Nat Neurosci 21:1038–1048

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Swarbrick S, Wragg N, Ghosh S et al (2019) Systematic Review of miRNA as Biomarkers in Alzheimer’s disease. Mol Neurobiol 56:6156–6167

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tabrizi SJ, Flower MD, Ross CA et al (2020) Huntington disease: new insights into molecular pathogenesis and therapeutic opportunities. Nat Rev Neurol 16:529–546

    Article  PubMed  Google Scholar 

  • Tang Y, Bao JS, Su JH et al (2017) MicroRNA-139 modulates Alzheimer’s-associated pathogenesis in SAMP8 mice by targeting cannabinoid receptor type 2. Genet Mol Res 16(1). https://doi.org/10.4238/gmr16019166

  • Torres AG, Batlle E, Ribas de Pouplana L (2014) Role of tRNA modifications in human diseases. Trends Mol Med 20:306–314

    Article  CAS  PubMed  Google Scholar 

  • Trixl L, Lusser A (2019) The dynamic RNA modification 5-methylcytosine and its emerging role as an epitranscriptomic mark. Wiley Interdiscip Rev RNA 10:e1510

    Article  PubMed  CAS  Google Scholar 

  • Urbanelli L, Emiliani C, Massini C et al (2008) Cathepsin D expression is decreased in Alzheimer’s disease fibroblasts. Neurobiol Aging 29:12–22

    Article  CAS  PubMed  Google Scholar 

  • Urbanelli L, Magini A, Polchi A et al (2011) Recent developments in therapeutic approaches for lysosomal storage diseases. Recent Pat CNS Drug Discov 6:1–19

    Article  CAS  PubMed  Google Scholar 

  • Ursu A, Vézina-Dawod S, Disney MD (2019) Methods to identify and optimize small molecules interacting with RNA (SMIRNAs). Drug Discov Today 24:2002–2016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Valdez G, Heyer MP, Feng G et al (2014) The role of muscle microRNAs in repairing the neuromuscular junction. PLoS One 9:e93140

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • van den Berg MMJ, Krauskopf J, Ramaekers JG et al (2020) Circulating microRNAs as potential biomarkers for psychiatric and neurodegenerative disorders. Prog Neurobiol 185:101732

    Article  PubMed  Google Scholar 

  • van der Lee SJ, Wolters FJ, Ikram MK et al (2018) The effect of APOE and other common genetic variants on the onset of Alzheimer’s disease and dementia: a community-based cohort study. Lancet Neurol 17:434–444

    Article  PubMed  Google Scholar 

  • van Es MA, Hardiman O, Chio A et al (2017) Amyotrophic lateral sclerosis. Lancet 390:2084–2098

    Article  PubMed  Google Scholar 

  • Vandivier LE, Gregory BD (2017) Reading the epitranscriptome: new techniques and perspectives. Enzymes 41:269–298

    Article  CAS  PubMed  Google Scholar 

  • Varghese S, Cotter M, Chevot F et al (2017) In vivo modification of tRNA with an artificial nucleobase leads to full disease remission in an animal model of multiple sclerosis. Nucleic Acids Res 45:2029–2039

    CAS  PubMed  Google Scholar 

  • Vassallo I, Zinn P, Lai M et al (2016) WIF1 re-expression in glioblastoma inhibits migration through attenuation of non-canonical WNT signaling by downregulating the lncRNA MALAT1. Oncogene 35:12–21

    Article  CAS  PubMed  Google Scholar 

  • Vieira AS, Dogini DB, Lopes-Cendes I (2018) Role of non-coding RNAs in non-aging-related neurological disorders. Braz J Med Biol Res 51:e7566

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vilardo E, Barbato C, Ciotti M et al (2010) MicroRNA-101 regulates amyloid precursor protein expression in hippocampal neurons. J Biol Chem 285:18344–18351

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Villar-Menéndez I, Porta S, Buira SP et al (2014) Increased striatal adenosine A2A receptor levels is an early event in Parkinson’s disease-related pathology and it is potentially regulated by miR-34b. Neurobiol Dis 69:206–214

    Article  PubMed  CAS  Google Scholar 

  • Visvanathan A, Patil V, Arora A et al (2018) Essential role of METTL3-mediated m6A modification in glioma stem-like cells maintenance and radioresistance. Oncogene 37:522–533

    Article  CAS  PubMed  Google Scholar 

  • Vrabec K, Boštjančič E, Koritnik B et al (2018) Differential expression of several miRNAs and the host genes AATK and DNM2 in leukocytes of sporadic ALS patients. Front Mol Neurosci 11:106

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wan G, Zhou W, Hu Y et al (2016) Transcriptional regulation of lncRNA genes by histone modification in Alzheimer’s disease. Biomed Res Int 2016:3164238

    Article  PubMed  PubMed Central  Google Scholar 

  • Wan Y-W, Al-Ouran R, Mangleburg CG et al (2020) Meta-analysis of the Alzheimer’s disease human brain transcriptome and functional dissection in mouse models. Cell Rep 32:107908

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang Z-H, Zhang J-L, Duan Y-L et al (2015) MicroRNA-214 participates in the neuroprotective effect of Resveratrol via inhibiting α-synuclein expression in MPTP-induced Parkinson’s disease mouse. Biomed Pharmacother 74:252–256

    Article  CAS  PubMed  Google Scholar 

  • Wang D-Q, Fu P, Yao C et al (2018a) Long non-coding RNAs, novel culprits, or bodyguards in neurodegenerative diseases. Mol Ther Nucleic Acids 10:269–276

    Article  CAS  PubMed  Google Scholar 

  • Wang Z, Xu P, Chen B et al (2018b) Identifying circRNA-associated-ceRNA networks in the hippocampus of Aβ1-42-induced Alzheimer’s disease-like rats using microarray analysis. Aging (Albany NY) 10:775–788

    Article  CAS  Google Scholar 

  • Wei C-W, Luo T, Zou S-S et al (2018) The role of long noncoding RNAs in central nervous system and neurodegenerative diseases. Front Behav Neurosci 12:175

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wei W, Wang Z-Y, Ma L-N et al (2020) MicroRNAs in Alzheimer’s disease: function and potential applications as diagnostic biomarkers. Front Mol Neurosci 13:160

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wen Y, Yu WH, Maloney B et al (2008) Transcriptional regulation of beta-secretase by p25/cdk5 leads to enhanced amyloidogenic processing. Neuron 57:680–690

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu Y-Y, Kuo H-C (2020) Functional roles and networks of non-coding RNAs in the pathogenesis of neurodegenerative diseases. J Biomed Sci 27:49

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wu P, Zuo X, Deng H et al (2013) Roles of long noncoding RNAs in brain development, functional diversification and neurodegenerative diseases. Brain Res Bull 97:69–80

    Article  CAS  PubMed  Google Scholar 

  • Wu D-M, Wen X, Wang Y-J et al (2018) Effect of microRNA-186 on oxidative stress injury of neuron by targeting interleukin 2 through the Janus kinase-signal transducer and activator of transcription pathway in a rat model of Alzheimer’s disease. J Cell Physiol 233:9488–9502

    Article  CAS  PubMed  Google Scholar 

  • Wu D-M, Wang S, Wen X et al (2019) Suppression of microRNA-342-3p increases glutamate transporters and prevents dopaminergic neuron loss through activating the Wnt signaling pathway via p21-activated kinase 1 in mice with Parkinson’s disease. J Cell Physiol 234:9033–9044

    Article  CAS  PubMed  Google Scholar 

  • Xie L, Mao M, Xiong K et al (2017) Circular RNAs: a novel player in development and disease of the central nervous system. Front Cell Neurosci 11:354

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Xing H, Guo S, Zhang Y et al (2016) Upregulation of microRNA-206 enhances lipopolysaccharide-induced inflammation and release of amyloid-β by targeting insulin-like growth factor 1 in microglia. Mol Med Rep 14:1357–1364

    Article  CAS  PubMed  Google Scholar 

  • Xiong X, Li X, Yi C (2018) N1-methyladenosine methylome in messenger RNA and non-coding RNA. Curr Opin Chem Biol 45:179–186

    Article  CAS  PubMed  Google Scholar 

  • Xu X, Wang Y, Liang H (2018) The role of A-to-I RNA editing in cancer development. Curr Opin Genet Dev 48:51–56

    Article  CAS  PubMed  Google Scholar 

  • Xylaki M, Atzler B, Outeiro TF (2019) Epigenetics of the synapse in neurodegeneration. Curr Neurol Neurosci Rep 19:72

    Article  PubMed  PubMed Central  Google Scholar 

  • Yan C, Wan R, Shi Y (2019) Molecular mechanisms of pre-mRNA splicing through structural biology of the spliceosome. Cold Spring Harb Perspect Biol 11:a032409

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang CH, Yue J, Pfeffer SR et al (2014) MicroRNA-21 promotes glioblastoma tumorigenesis by down-regulating insulin-like growth factor-binding protein-3 (IGFBP3). J Biol Chem 289:25079–25087

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang G, Song Y, Zhou X et al (2015) MicroRNA-29c targets β-site amyloid precursor protein-cleaving enzyme 1 and has a neuroprotective role in vitro and in vivo. Mol Med Rep 12:3081–3088

    Article  CAS  PubMed  Google Scholar 

  • Yang CP, Zhang ZH, Zhang LH et al (2016) Neuroprotective role of microRNA-22 in a 6-hydroxydopamine-induced cell model of Parkinson’s disease via regulation of its target gene TRPM7. J Mol Neurosci 60:445–452

    Article  CAS  PubMed  Google Scholar 

  • Yang X, Liu M, Li M et al (2020) Epigenetic modulations of noncoding RNA: a novel dimension of Cancer biology. Mol Cancer 19:64

    Article  PubMed  PubMed Central  Google Scholar 

  • Yeasmin F, Yada T, Akimitsu N (2018) Micropeptides encoded in transcripts previously identified as long noncoding RNAs: a new chapter in transcriptomics and proteomics. Front Genet 9:144

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zendjabil M (2018) Circulating microRNAs as novel biomarkers of Alzheimer’s disease. Clin Chim Acta 484:99–104

    Article  CAS  PubMed  Google Scholar 

  • Zetterberg H, Burnham SC (2019) Blood-based molecular biomarkers for Alzheimer’s disease. Mol Brain 12:26

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhang Z, Cheng Y (2014) miR-16-1 promotes the aberrant α-synuclein accumulation in Parkinson disease via targeting heat shock protein 70. Sci World J 2014:938348

    Google Scholar 

  • Zhang C, Jia G (2018) Reversible RNA modification N1-methyladenosine (m1A) in mRNA and tRNA. Genomics Proteomics Bioinf 16:155–161

    Article  Google Scholar 

  • Zhang C-Z, Zhang J-X, Zhang A-L et al (2010) MiR-221 and miR-222 target PUMA to induce cell survival in glioblastoma. Mol Cancer 9:229

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhang J, Hu M, Teng Z et al (2014) Synaptic and cognitive improvements by inhibition of 2-AG metabolism are through upregulation of microRNA-188-3p in a mouse model of Alzheimer’s disease. J Neurosci 34:14919–14933

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhang B, Chen C-F, Wang A-H et al (2015a) MiR-16 regulates cell death in Alzheimer’s disease by targeting amyloid precursor protein. Eur Rev Med Pharmacol Sci 19:4020–4027

    CAS  PubMed  Google Scholar 

  • Zhang Y, Han D, Wei W et al (2015b) MiR-218 inhibited growth and metabolism of human glioblastoma cells by directly targeting E2F2. Cell Mol Neurobiol 35:1165–1173

    Article  CAS  PubMed  Google Scholar 

  • Zhang B, Wang L-L, Ren R-J et al (2016) MicroRNA-146a represses LRP2 translation and leads to cell apoptosis in Alzheimer’s disease. FEBS Lett 590:2190–2200

    Article  CAS  PubMed  Google Scholar 

  • Zhang S, Zhu D, Li H et al (2017) Characterization of circRNA-associated-ceRNA networks in a senescence-accelerated mouse prone 8 brain. Mol Ther 25:2053–2061

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang Y-H, Bai S-F, Yan J-Q (2019) Blood circulating miRNAs as biomarkers of Alzheimer’s disease: a systematic review and meta-analysis. Biomark Med 13:1045–1054

    Article  CAS  PubMed  Google Scholar 

  • Zhang Y, Xia Q, Lin J (2020) LncRNA H19 attenuates apoptosis in MPTP-Induced Parkinson’s disease through regulating miR-585-3p/PIK3R3. Neurochem Res 45:1700–1710

    Article  CAS  PubMed  Google Scholar 

  • Zhao Z-B, Wu L, Xiong R et al (2014) MicroRNA-922 promotes tau phosphorylation by downregulating ubiquitin carboxy-terminal hydrolase L1 (UCHL1) expression in the pathogenesis of Alzheimer’s disease. Neuroscience 275:232–237

    Article  CAS  PubMed  Google Scholar 

  • Zhao Y, Alexandrov PN, Jaber V et al (2016) Deficiency in the ubiquitin conjugating enzyme UBE2A in Alzheimer’s disease (AD) is linked to deficits in a natural circular miRNA-7 sponge (circRNA; ciRS-7). Genes (Basel) 7:116

    Article  CAS  Google Scholar 

  • Zhao Y, Dunker W, Yu Y-T et al (2018) The role of noncoding RNA pseudouridylation in nuclear gene expression events. Front Bioeng Biotechnol 6:8

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhao M-Y, Wang G-Q, Wang N-N et al (2019) The long-non-coding RNA NEAT1 is a novel target for Alzheimer’s disease progression via miR-124/BACE1 axis. Neurol Res 41:489–497

    Article  PubMed  Google Scholar 

  • Zhou C, Molinie B, Daneshvar K et al (2017) Genome-wide maps of m6A circRNAs identify widespread and cell-type-specific methylation patterns that are distinct from mRNAs. Cell Rep 20:2262–2276

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou Y, Wang Z-F, Li W et al (2018) Protective effects of microRNA-330 on amyloid β-protein production, oxidative stress, and mitochondrial dysfunction in Alzheimer’s disease by targeting VAV1 via the MAPK signaling pathway. J Cell Biochem 119:5437–5448

    Article  CAS  PubMed  Google Scholar 

  • Zhou Y, Deng J, Chu X et al (2019) Role of post-transcriptional control of calpain by miR-124-3p in the development of Alzheimer’s disease. J Alzheimers Dis 67:571–581

    Article  CAS  PubMed  Google Scholar 

  • Zhu Z-M, Huo F-C, Pei D-S (2020) Function and evolution of RNA N6-methyladenosine modification. Int J Biol Sci 16:1929–1940

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zimmer-Bensch G (2019) Emerging roles of long non-coding RNAs as drivers of brain evolution. Cells 8:1399

    Article  CAS  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Carla Emiliani .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2021 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Calzoni, E. et al. (2021). RNA Modifications in Neurodegenerations. In: Jurga, S., Barciszewski, J. (eds) Epitranscriptomics. RNA Technologies, vol 12. Springer, Cham. https://doi.org/10.1007/978-3-030-71612-7_2

Download citation

Publish with us

Policies and ethics