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Non-coding RNAs in Alzheimer's Disease

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Abstract

Alzheimer's disease (AD) is a complex neurodegenerative disorder and the most common dementia among the elderly. Accumulating research indicates that noncoding RNAs (ncRNAs), especially microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), are increasingly being implicated in AD. MiRNAs are conserved small ncRNAs that control gene expression post-transcriptionally while lncRNAs function in many ways. Recent profiling research in human or mouse models suggests that miRNAs are aberrantly expressed in AD, and these have been implicated in the regulation of amyloid-β (Aβ) peptide, tau, inflammation, cell death, and other aspects which are the main pathomechanisms of AD. In addition, regulation of miRNAs varies in blood, and cerebral spinal fluid may indicate alterations in AD. Together with brain-specific miRNAs, these miRNAs could be potential AD biomarkers. All the above may provide the basis for new approaches for AD. Here, we review current findings regarding ncRNA research in human and mouse models to provide a strong basis for future study aiming at promising contributions of ncRNA in AD.

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References

  1. Palop JJ, Chin J, Mucke L (2006) A network dysfunction perspective on neurodegenerative diseases. Nature 443:768–773

    Article  PubMed  CAS  Google Scholar 

  2. Walsh DM, Minogue AM, Sala Frigerio C, Fadeeva JV, Wasco W, Selkoe DJ (2007) The APP family of proteins: similarities and differences. Biochem Soc Trans 35:416–420

    Article  PubMed  CAS  Google Scholar 

  3. Singer O, Marr RA, Rockenstein E, Crews L, Coufal NG, Gage FH, Verma IM, Masliah E (2005) Targeting BACE1 with siRNAs ameliorates Alzheimer disease neuropathology in a transgenic model. Nat Neurosci 8:1343–1349

    Article  PubMed  CAS  Google Scholar 

  4. Duyckaerts C, Delatour B, Potier MC (2009) Classification and basic pathology of Alzheimer disease. Acta Neuropathol 118:5–36

    Article  PubMed  CAS  Google Scholar 

  5. Palop JJ, Mucke L (2010) Amyloid-beta-induced neuronal dysfunction in Alzheimer's disease: from synapses toward neural networks. Nat Neurosci 13:812–818

    Article  PubMed  CAS  Google Scholar 

  6. Bertram L, Lill CM, Tanzi RE (2010) The genetics of Alzheimer disease: back to the future. Neuron 68:270–281

    Article  PubMed  CAS  Google Scholar 

  7. Genin E, Hannequin D, Wallon D, Sleegers K, Hiltunen M, Combarros O et al (2011) APOE and Alzheimer disease: a major gene with semi-dominant inheritance. Mol Psychiatry 16:903–907

    Article  PubMed  CAS  Google Scholar 

  8. Logue MW, Schu M, Vardarajan BN, Buros J, Green RC, Go RC, Griffith P, Obisesan TO, Shatz R, Borenstein A, Cupples LA, Lunetta KL, Fallin MD, Baldwin CT, Farrer LA, Multi-Institutional Research on Alzheimer Genetic Epidemiology (MIRAGE) Study Group (2011) A comprehensive genetic association study of Alzheimer disease in African Americans. Arch Neurol 68:1569–1579

    Article  PubMed  Google Scholar 

  9. Vollmar P, Kullmann JS, Thilo B, Claussen MC, Rothhammer V, Jacobi H, Sellner J, Nessler S, Korn T, Hemmer B (2010) Active immunization with amyloid-beta 142 impairs memory performance through TLR2/4-dependent activation of the innate immune system. J Immunol 185:6338–6347

    Article  PubMed  CAS  Google Scholar 

  10. Morales I, Farías G, Maccioni RB (2010) Neuroimmunomodulation in the pathogenesis of Alzheimer's disease. Neuroimmunomodulation 17:202–204

    Article  PubMed  CAS  Google Scholar 

  11. Jones L, Holmans PA, Hamshere ML, Harold D, Moskvina V, Ivanov D (2010) Genetic evidence implicates the immune system and cholesterol metabolism in the aetiology of Alzheimer's disease. PLoS One 5:e13950

    Article  PubMed  CAS  Google Scholar 

  12. Boutajangout A, Quartermain D, Sigurdsson EM (2010) Immunotherapy targeting pathological tau prevents cognitive decline in a new tangle mouse model. J Neurosci 30:16559–16566

    Article  PubMed  CAS  Google Scholar 

  13. Kapranov P, Cheng J, Dike S, Nix DA, Duttagupta R, Willingham AT, Stadler PF, Hertel J, Hackermüller J, Hofacker IL, Bell I, Cheung E, Drenkow J, Dumais E, Patel S, Helt G, Ganesh M, Ghosh S, Piccolboni A, Sementchenko V, Tammana H, Gingeras TR (2007) RNA maps reveal new RNA classes and a possible function for pervasive transcription. Science 316:1484–1488

    Article  PubMed  CAS  Google Scholar 

  14. Berretta J, Morillon (2009) A pervasive transcription constitutes a new level of eukaryotic genome regulation. EMBO Rep 10:973–982

    Article  PubMed  CAS  Google Scholar 

  15. Pollard KS, Salama SR, Lambert N, Lambot MA, Coppens S, Pedersen JS, Katzman S, King B, Onodera C, Siepel A, Kern AD, Dehay C, Igel H, Ares M Jr, Vanderhaeghen P, Haussler D (2006) An RNA gene expressed during cortical development evolved rapidly in human. Nature 443:167–172

    Article  PubMed  CAS  Google Scholar 

  16. Majer A, Booth SA (2010) Computational methodologies for studying non-coding RNAs relevant to central nervous system function and dysfunction. Brain Res 1338:131–145

    Article  PubMed  CAS  Google Scholar 

  17. Yang JH, Shao P, Zhou H, Chen YQ, Qu LH (2010) DeepBase: a database for deeply annotating and mining deep sequencing data. Nucleic Acids Res 38:123–130

    Article  CAS  Google Scholar 

  18. Brosius J (2005) Waste not, want not—transcript excess in multicellular eukaryotes. Trends Genet 21:287–288

    Article  PubMed  CAS  Google Scholar 

  19. Faghihi MA, Modarresi F, Khalil AM, Wood DE, Sahagan BG, Morgan TE, Finch CE, St Laurent G 3rd, Kenny PJ, Wahlestedt C (2008) Expression of a non-coding RNA is elevated in Alzheimer's disease and drives rapid feed-forward regulation of beta-secretase. Nat Med 14:723–730

    Article  PubMed  CAS  Google Scholar 

  20. Cao X, Yeo G, Muotri AR, Kuwabara T, Gage FH (2006) Noncoding RNAs in the mammalian central nervous system. Annu Rev Neurosci 29:77–103

    Article  PubMed  CAS  Google Scholar 

  21. Mehler MF, Mattick JS (2007) Noncoding RNAs and RNA editing in brain development, functional diversification, and neurological disease. Physiol Rev 87:799–823

    Article  PubMed  CAS  Google Scholar 

  22. Mercer TR, Dinger ME, Mariani J, Kosik KS, Mehler MF, Mattick JS (2008) Noncoding RNAs in long-term memory formation. Neuroscientist 14:434–445

    Article  PubMed  CAS  Google Scholar 

  23. Tsurudome K, Tsang K, Liao EH, Ball R, Penney J, Yang JS, Elazzouzi F, He T, Chishti A, Lnenicka G, Lai EC, Haghighi AP (2010) The Drosophila miR-310 cluster negatively regulates synaptic strength at the neuromuscular junction. Neuron 68:879–893

    Article  PubMed  CAS  Google Scholar 

  24. Gao FB (2010) Context-dependent functions of specific microRNAs in neuronal development. Neural Dev 5:25

    Article  PubMed  CAS  Google Scholar 

  25. Qureshi IA, Mehler MF (2011) Non-coding RNA networks underlying cognitive disorders across the lifespan. Trends Mol Med 17:337–346

    Article  PubMed  CAS  Google Scholar 

  26. Siegel G, Saba R, Schratt G (2011) MicroRNAs in neurons: manifold regulatory roles at the synapse. Curr Opin Genet Dev 21:491–497

    Article  PubMed  CAS  Google Scholar 

  27. Mouse Genome Sequencing Consortium, Waterston RH, Lindblad-Toh K, Birney E, Rogers J, Abril JF, Agarwal P et al (2002) Initial sequencing and comparative analysis of the mouse genome. Nature 420:520–562

    Article  PubMed  CAS  Google Scholar 

  28. Mattick JS, Makunin IV (2006) Non-coding RNA. Hum Mol Genet 15:17–29

    Article  CAS  Google Scholar 

  29. Mattick JS, Makunin IV (2005) Small regulatory RNAs in mammals. Hum Mol Genet 14:121–132

    Article  CAS  Google Scholar 

  30. Willingham AT, Orth AP, Batalov S, Peters EC, Wen BG, Aza-Blanc P, Hogenesch JB, Schultz PG (2005) A strategy for probing the function of noncoding RNAs finds a repressor of NFAT. Science 309:1570–1573

    Article  PubMed  CAS  Google Scholar 

  31. Mattick JS (2011) The central role of RNA in human development and cognition. FEBS Lett 585:1600–1616

    Article  PubMed  CAS  Google Scholar 

  32. Nakamori M, Thornton C (2010) Epigenetic changes and non-coding expanded repeats. Neurobiol Dis 39:21–27

    Article  PubMed  CAS  Google Scholar 

  33. Shao NY, Hu HY, Yan Z, Xu Y, Hu H, Menzel C, Li N, Chen W, Khaitovich P (2010) Comprehensive survey of human brain microRNA by deep sequencing. BMC Genomics 11:409

    Article  PubMed  CAS  Google Scholar 

  34. Babiarz JE, Hsu R, Melton C, Thomas M, Ullian EM, Blelloch R (2011) A role for noncanonical microRNAs in the mammalian brain revealed by phenotypic differences in Dgcr8 versus Dicer1 knockouts and small RNA sequencing. RNA 17:1489–14501

    Article  PubMed  CAS  Google Scholar 

  35. Baek D, Villén J, Shin C, Camargo FD, Gygi SP, Bartel DP (2008) The impact of microRNAs on protein output. Nature 455:64–71

    Article  PubMed  CAS  Google Scholar 

  36. Selbach M, Schwanhäusser B, Thierfelder N, Fang Z, Khanin R, Rajewsky N (2008) Widespread changes in protein synthesis induced by microRNAs. Nature 455:58–63

    Article  PubMed  CAS  Google Scholar 

  37. Hugon J, Paquet C (2008) Targeting miRNAs in Alzheimer's disease. Expert Rev Neurother 8:1615–1616

    Article  PubMed  Google Scholar 

  38. Klein ME, Impey S, Goodman RH (2005) Role reversal: the regulation of neuronal gene expression by microRNAs. Curr Opin Neurobiol 15:507–513

    Article  PubMed  CAS  Google Scholar 

  39. Zamore PD, Haley B (2005) Ribo-gnome: the big world of small RNAs. Science 309:1519–1524

    Article  PubMed  CAS  Google Scholar 

  40. Kosik KS, Krichevsky AM (2005) The elegance of the MicroRNAs: a neuronal perspective. Neuron 47:779–782

    Article  PubMed  CAS  Google Scholar 

  41. Filipowicz W (2005) RNAi: the nuts and bolts of the RISC machine. Cell 122:17–20

    Article  PubMed  CAS  Google Scholar 

  42. Miranda KC, Huynh T, Tay Y, Ang YS, Tam WL, Thomson AM, Lim B, Rigoutsos I (2006) A pattern-based method for the identification of microRNA binding sites and their corresponding heteroduplexes. Cell 126:1203–1217

    Article  PubMed  CAS  Google Scholar 

  43. Schaeffer C, Beaulande M, Ehresmann C, Ehresmann B, Moine H (2003) The RNA binding protein FMRP: new connections and missing links. Biol Cell 95:221–228

    Article  PubMed  CAS  Google Scholar 

  44. Qi Y, Denli AM, Hannon GJ (2005) Biochemical specialization within Arabidopsis RNA silencing pathways. Mol Cell 19:421–428

    Article  PubMed  CAS  Google Scholar 

  45. Mercer TR, Dinger ME, Mattick JS (2009) Long non-coding RNAs: insights into functions. Nat Rev Genet 10:155–159

    Article  PubMed  CAS  Google Scholar 

  46. Ponting CP, Oliver PL, Reik W (2009) Evolution and functions of long noncoding RNAs. Cell 136:629–641

    Article  PubMed  CAS  Google Scholar 

  47. Brosnan CA, Voinnet O (2009) The long and the short of noncoding RNAs. Curr Opin Cell Biol 21:416–425

    Article  PubMed  CAS  Google Scholar 

  48. ENCODE Project Consortium, Birney E, Stamatoyannopoulos JA, Dutta A, Guigó R, Gingeras TR et al (2007) Identification and analysis of functional elements in 1 % of the human genome by the ENCODE pilot project. Nature 447:799–816

    Article  PubMed  CAS  Google Scholar 

  49. Dinger ME, Pang KC, Mercer TR, Crowe ML, Grimmond SM, Mattick JS (2009) NRED: a database of long noncoding RNA expression. Nucleic Acids Res 37(Database issue):D122–D126

    Article  PubMed  CAS  Google Scholar 

  50. Lindberg J, Lundeberg J (2010) The plasticity of the mammalian transcriptome. Genomics 95:1–6

    Article  PubMed  CAS  Google Scholar 

  51. Hébert SS, Sergeant N, Buée L (2012) MicroRNAs and the regulation of tau metabolism. Int J Alzheimers Dis 2012:406561

    PubMed  Google Scholar 

  52. Hébert SS, Papadopoulou AS, Smith P, Galas MC, Planel E, Silahtaroglu AN, Sergeant N, Buée L, De Strooper B (2010) Genetic ablation of Dicer in adult forebrain neurons results in abnormal tau hyperphosphorylation and neurodegeneration. Hum Mol Genet 19:3959–3969

    Article  PubMed  CAS  Google Scholar 

  53. Cogswell JP, Ward J, Taylor IA, Waters M, Shi Y, Cannon B, Kelnar K, Kemppainen J, Brown D, Chen C, Prinjha RK, Richardson JC, Saunders AM, Roses AD, Richards CA (2008) Identification of miRNA changes in Alzheimer's disease brain and CSF yields putative biomarkers and insights into disease pathways. J Alzheimers Dis 14:27–41

    PubMed  CAS  Google Scholar 

  54. Lukiw WJ (2007) Micro-RNA speciation in fetal, adult and Alzheimer's disease hippocampus. Neuroreport 18:297–300

    Article  PubMed  CAS  Google Scholar 

  55. Wang WX, Rajeev BW, Stromberg AJ, Ren N, Tang G, Huang Q, Rigoutsos I, Nelson PT (2008) The expression of microRNA miR-107 decreases early in Alzheimer's disease and may accelerate disease progression through regulation of beta-site amyloid precursor protein-cleaving enzyme 1. J Neurosci 28:1213–1223

    Article  PubMed  CAS  Google Scholar 

  56. Hébert SS, Horré K, Nicolaï L, Papadopoulou AS, Mandemakers W, Silahtaroglu AN, Kauppinen S, Delacourte A, De Strooper B (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 U S A 105:6415–6420

    Article  PubMed  Google Scholar 

  57. Nunez-Iglesias J, Liu CC, Morgan TE, Finch CE, Zhou XJ (2010) Joint genome-wide profiling of miRNA and mRNA expression in Alzheimer's disease cortex reveals altered miRNA regulation. PLoS One 5:e8898

    Article  PubMed  CAS  Google Scholar 

  58. Geekiyanage H, Chan C (2011) MicroRNA-137/181c regulates serine palmitoyltransferase and in turn amyloid β, novel targets in sporadic Alzheimer's disease. J Neurosci 31:14820–14830

    Article  PubMed  CAS  Google Scholar 

  59. Shioya M, Obayashi S, Tabunoki H, Arima K, Saito Y, Ishida T, Satoh J (2010) Aberrant microRNA expression in the brains of neurodegenerative diseases: miR-29a decreased in Alzheimer disease brains targets neurone navigator 3. Neuropathol Appl Neurobiol 36:320–330

    Article  PubMed  CAS  Google Scholar 

  60. Hébert SS, Horré K, Nicolaï L, Bergmans B, Papadopoulou AS, Delacourte A, De Strooper B (2009) MicroRNA regulation of Alzheimer's amyloid precursor protein expression. Neurobiol Dis 33:422–428

    Article  PubMed  CAS  Google Scholar 

  61. Sethi P, Lukiw WJ (2009) Micro-RNA abundance and stability in human brain: specific alterations in Alzheimer's disease temporal lobe neocortex. Neurosci Lett 459:100–104

    Article  PubMed  CAS  Google Scholar 

  62. Schipper HM, Maes OC, Chertkow HM, Wang E (2007) MicroRNA expression in Alzheimer blood mononuclear cells. Gene Regul Syst Bio 1:263–274

    PubMed  Google Scholar 

  63. Villa C, Fenoglio C, De Riz M, Clerici F, Marcone A, Benussi L, Ghidoni R, Gallone S, Cortini F, Serpente M, Cantoni C, Fumagalli G, Martinelli Boneschi F, Cappa S, Binetti G, Franceschi M, Rainero I, Giordana MT, Mariani C, Bresolin N, Scarpini E, Galimberti D (2011) Role of hnRNP-A1 and miR-590-3p in neuronal death: genetics and expression analysis in patients with Alzheimer disease and frontotemporal lobar degeneration. Rejuvenation Res 14:275–281

    Article  PubMed  CAS  Google Scholar 

  64. Siegel G, Obernosterer G, Fiore R, Oehmen M, Bicker S, Christensen M, Khudayberdiev S, Leuschner PF, Busch CJ, Kane C, Hübel K, Dekker F, Hedberg C, Rengarajan B, Drepper C, Waldmann H, Kauppinen S, Greenberg ME, Draguhn A, Rehmsmeier M, Martinez J, Schratt GM (2009) A functional screen implicates microRNA-138-dependent regulation of the depalmitoylation enzyme APT1 in dendritic spine morphogenesis. Nat Cell Biol 11:705–716

    Article  PubMed  CAS  Google Scholar 

  65. Zovoilis A, Agbemenyah HY, Agis-Balboa RC, Stilling RM, Edbauer D, Rao P, Farinelli L, Delalle I, Schmitt A, Falkai P, Bahari-Javan S, Burkhardt S, Sananbenesi F, Fischer A (2011) MicroRNA-34c is a novel target to treat dementias. EMBO J 30:4299–4308

    Article  PubMed  CAS  Google Scholar 

  66. Wang X, Liu P, Zhu H, Xu Y, Ma C, Dai X, Huang L, Liu Y, Zhang L, Qin C (2009) MiR-34a, a microRNA up-regulated in a double transgenic mouse model of Alzheimer's disease, inhibits bcl2 translation. Brain Res Bull 80:268–273

    Article  PubMed  CAS  Google Scholar 

  67. Kole AJ, Swahari V, Hammond SM, Deshmukh M (2011) MiR-29b is activated during neuronal maturation and targets BH3-only genes to restrict apoptosis. Genes Dev 25:125–130

    Article  PubMed  CAS  Google Scholar 

  68. Ling KH, Brautigan PJ, Hahn CN, Daish T, Rayner JR, Cheah PS, Raison JM, Piltz S, Mann JR, Mattiske DM, Thomas PQ, Adelson DL, Scott HS (2011) Deep sequencing analysis of the developing mouse brain reveals a novel microRNA. BMC Genomics 12:176

    Article  PubMed  CAS  Google Scholar 

  69. Boissonneault V, Plante I, Rivest S, Provost P (2009) MicroRNA-298 and microRNA-328 regulate expression of mouse beta-amyloid precursor protein-converting enzyme 1. J Biol Chem 284:1971–1981

    Article  PubMed  CAS  Google Scholar 

  70. Long JM, Lahiri DK (2011) MicroRNA-101 downregulates Alzheimer's amyloid-β precursor protein levels in human cell cultures and is differentially expressed. Biochem Biophys Res Commun 404:889–895

    Article  PubMed  CAS  Google Scholar 

  71. Zong Y, Wang H, Dong W, Quan X, Zhu H, Xu Y, Huang L, Ma C, Qin C (2011) MiR-29c regulates BACE1 protein expression. Brain Res 1395:108–115

    Article  PubMed  CAS  Google Scholar 

  72. Wang WX, Huang Q, Hu Y, Stromberg AJ, Nelson PT (2011) Patterns of microRNA expression in normal and early Alzheimer's disease human temporal cortex: white matter versus gray matter. Acta Neuropathol 121:193–205

    Article  PubMed  Google Scholar 

  73. Wang WX, Wilfred BR, Madathil SK, Tang G, Hu Y, Dimayuga J, Stromberg AJ, Huang Q, Saatman KE, Nelson PT (2010) MiR-107 regulates granulin/progranulin with implications for traumatic brain injury and neurodegenerative disease. Am J Pathol 177:334–345

    Article  PubMed  CAS  Google Scholar 

  74. Provost P (2010) Interpretation and applicability of microRNA data to the context of Alzheimer's and age-related diseases. Aging (Albany NY) 2:166–169

    CAS  Google Scholar 

  75. Bettens K, Brouwers N, Engelborghs S, Van Miegroet H, De Deyn PP, Theuns J, Sleegers K, Van Broeckhoven C (2009) APP and BACE1 miRNA genetic variability has no major role in risk for Alzheimer disease. Hum Mutat 30:1207–1213

    Article  PubMed  CAS  Google Scholar 

  76. Schonrock N, Ke YD, Humphreys D, Staufenbiel M, Ittner LM, Preiss T, Götz J (2010) Neuronal microRNA deregulation in response to Alzheimer's disease amyloid-beta. PLoS One 5:e11070

    Article  PubMed  CAS  Google Scholar 

  77. Wang JZ, Grundke-Iqbal I, Iqbal K (2007) Kinases and phosphatases and tau sites involved in Alzheimer neurofibrillary degeneration. Eur J Neurosci 25:59–68

    Article  PubMed  Google Scholar 

  78. Lewis J, Dickson DW, Lin WL, Chisholm L, Corral A, Jones G, Yen SH, Sahara N, Skipper L, Yager D, Eckman C, Hardy J, Hutton M, McGowan E (2001) Enhanced neurofibrillary degeneration in transgenic mouse expressing mutant tau and APP. Science 293:1487–1491

    Article  PubMed  CAS  Google Scholar 

  79. Bilen J, Liu N, Burnett BG, Pittman RN, Bonini NM (2006) MicroRNA pathways modulate polyglutamine-induced neurodegeneration. Mol Cell 24:157–163

    Article  PubMed  CAS  Google Scholar 

  80. Carrettiero DC, Hernandez I, Neveu P, Papagiannakopoulos T, Kosik KS (2009) The cochaperone BAG2 sweeps paired helical filament- insoluble tau from the microtubule. J Neurosci 29:2151–2161

    Article  PubMed  CAS  Google Scholar 

  81. Smith PY, Delay C, Girard J, Papon MA, Planel E, Sergeant N, Buée L, Hébert SS (2011) MicroRNA-132 loss is associated with tau exon 10 inclusion in progressive supranuclear palsy. Hum Mol Genet 20:4016–4024

    Article  PubMed  CAS  Google Scholar 

  82. Julien C, Tremblay C, Emond V, Lebbadi M, Salem N Jr, Bennett DA, Calon F (2009) Sirtuin 1 reduction parallels the accumulation of tau in Alzheimer disease. J Neuropathol Exp Neurol 68:48–58

    Article  PubMed  CAS  Google Scholar 

  83. Ramachandran D, Roy U, Garg S, Ghosh S, Pathak S, Kolthur-Seetharam U (2011) Sirt1 and mir-9 expression is regulated during glucose-stimulated insulin secretion in pancreatic β-islets. FEBS J 278:1167–1174

    Article  PubMed  CAS  Google Scholar 

  84. Saba R, Goodman CD, Huzarewich RL, Robertson C, Booth SA (2008) A miRNA signature of prion induced neurodegeneration. PLoS One 3:e3652

    Article  PubMed  CAS  Google Scholar 

  85. Ponomarev ED, Veremeyko T, Barteneva N, Krichevsky AM, Weiner HL (2011) MicroRNA-124 promotes microglia quiescence and suppresses EAE by deactivating macrophages via the C/EBP-α-PU.1 pathway. Nat Med 17:64–70

    Article  PubMed  CAS  Google Scholar 

  86. Taganov KD, Boldin MP, Chang KJ, Baltimore D (2006) NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci U S A 103:12481–12486

    Article  PubMed  CAS  Google Scholar 

  87. Perry MM, Williams AE, Tsitsiou E, Larner-Svensson HM, Lindsay MA (2009) Divergent intracellular pathways regulate interleukin-1beta-induced miR-146a and miR-146b expression and chemokine release in human alveolar epithelial cells. FEBS Lett 583:3349–3355

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  89. 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  PubMed  CAS  Google Scholar 

  90. Wang LL, Huang Y, Wang G, Chen SD (2012) The potential role of microRNA-146 in Alzheimer's disease: biomarker or therapeutic target? Med Hypotheses 78:398–401

    Article  PubMed  CAS  Google Scholar 

  91. Lee YJ, Han SB, Nam SY, Oh KW, Hong JT (2010) Inflammation and Alzheimer's disease. Arch Pharm Res 33:1539–1556

    Article  PubMed  CAS  Google Scholar 

  92. Wee Yong V (2010) Inflammation in neurological disorders: a help or a hindrance? Neuroscientist 16:408–420

    Article  PubMed  CAS  Google Scholar 

  93. Salminen A, Kauppinen A, Suuronen T, Kaarniranta K, Ojala J (2009) ER stress in Alzheimer's disease: a novel neuronal trigger for inflammation and Alzheimer's pathology. J Neuroinflammation 6:41

    Article  PubMed  CAS  Google Scholar 

  94. Smith P, Al Hashimi A, Girard J, Delay C, Hébert SS (2011) In vivo regulation of amyloid precursor protein neuronal splicing by microRNAs. J Neurochem 116:240–247

    Article  PubMed  CAS  Google Scholar 

  95. Lee JH, Cheon YH, Woo RS, Song DY, Moon C, Baik TK (2012) Evidence of early involvement of apoptosis inducing factor-induced neuronal death in Alzheimer brain. Anat Cell Biol 45:26–37

    Article  PubMed  Google Scholar 

  96. Xu P, Guo M, Hay BA (2004) MicroRNAs and the regulation of cell death. Trends Genet 20:617–624

    Article  PubMed  CAS  Google Scholar 

  97. Fang M, Wang J, Zhang X, Geng Y, Hu Z, Rudd JA, Ling S, Chen W, Han S (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  PubMed  CAS  Google Scholar 

  98. Cimmino A, Calin GA, Fabbri M, Iorio MV, Ferracin M, Shimizu M, Wojcik SE, Aqeilan RI, Zupo S, Dono M, Rassenti L, Alder H, Volinia S, Liu CG, Kipps TJ, Negrini M, Croce CM (2005) MiR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci U S A 102:13944–13949

    Article  PubMed  CAS  Google Scholar 

  99. 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 (2011) 17A, a novel non-coding RNA, regulates GABA B alternative splicing and signaling in response to inflammatory stimuli and in Alzheimer disease. Neurobiol Dis 41:308–317

    Article  PubMed  CAS  Google Scholar 

  100. Mus E, Hof PR, Tiedge H (2007) Dendritic BC200 RNA in aging and in Alzheimer's disease. Proc Natl Acad Sci U S A 104:10679–10684

    Article  PubMed  CAS  Google Scholar 

  101. Lukiw WJ, Handley P, Wong L, Crapper McLachlan DR (1992) BC200 RNA in normal human neocortex, non-Alzheimer dementia (NAD), and senile dementia of the Alzheimer type (AD). Neurochem Res 17:591–597

    Article  PubMed  CAS  Google Scholar 

  102. Li JS, Yao ZX (2012) MicroRNAs: novel regulators of oligodendrocyte differentiation and potential therapeutic targets in demyelination-related diseases. Mol Neurobiol 45:200–212

    Article  PubMed  CAS  Google Scholar 

  103. Rogaev EI (2005) Small RNAs in human brain development and disorders. Biochemistry (Mosc) 70:1404–1407

    Article  CAS  Google Scholar 

  104. Delay C, Hébert SS (2011) MicroRNAs and Alzheimer's disease mouse models: current insights and future research avenues. Int J Alzheimers Dis 2011:894938

    PubMed  Google Scholar 

  105. Junn E, Mouradian MM (2012) MicroRNAs in neurodegenerative diseases and their therapeutic potential. Pharmacol Ther 133:142–150

    Article  PubMed  CAS  Google Scholar 

  106. Alvarez-Erviti L, Seow Y, Yin H, Betts C, Lakhal S, Wood MJ (2011) Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol 29:341–345

    Article  PubMed  CAS  Google Scholar 

  107. Geekiyanage H, Jicha GA, Nelson PT, Chan C (2012) Blood serum miRNA: non-invasive biomarkers for Alzheimer's disease. Exp Neurol 235:491–496

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (81000544, 81171209), the Shandong Provincial Natural Science Foundation, China (ZR2010HQ004, ZR2011HZ001), the Medicine and Health Science Technology Development Project of Shandong Province (2011WSA02018, 2011WSA02020), the Project supported by the Qingdao Bureau of Science and Technology (10-3-3-4-19-nsh, 11-2-3-2-(1)-nsh), and the Shandong Provincial Outstanding Medical Academic Professional Program.

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  1. Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, No.5 Donghai Middle Road, Qingdao, Shandong Province, 266071, China

    Lin Tan, Jin-Tai Yu, Nan Hu & Lan Tan

  2. College of Medicine and Pharmaceutics, Ocean University of China, Qingdao, 266003, People’s Republic of China

    Jin-Tai Yu & Lan Tan

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  2. Jin-Tai Yu
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  3. Nan Hu
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  4. Lan Tan
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Correspondence to Jin-Tai Yu or Lan Tan.

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Tan, L., Yu, JT., Hu, N. et al. Non-coding RNAs in Alzheimer's Disease. Mol Neurobiol 47, 382–393 (2013). https://doi.org/10.1007/s12035-012-8359-5

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  • DOI: https://doi.org/10.1007/s12035-012-8359-5

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