Molecular Biology Reports

, Volume 43, Issue 11, pp 1193–1204 | Cite as

The roles of non-coding RNAs in Parkinson’s disease

  • Maryam Majidinia
  • Aynaz Mihanfar
  • Reza Rahbarghazi
  • Alireza Nourazarian
  • BakiyeGoker Bagca
  • Çığır Biray Avci


Parkinson’s disease (PD) is considered as a high prevalence neurodegenerative disorders worldwide. Pathologically, the demise of dopamine-producing cells, in large part due to an abnormal accumulation of the α-synuclein in the substantia nigra, is one of the main causes of the disease. Up until now, many de novo investigations have been conducted to disclose the mechanisms underlying in PD. Among them, impacts of non-coding RNAs (ncRNAs) on the pathogenesis and/or progression of PD need to be highlighted. microRNAs (miRNAs) and long ncRNAs (lncRNAs) are more noteworthy in this context. miRNAs are small ncRNAs (with 18–25 nucleotide in length) that control the expression of multiple genes at post-transcriptional level, while lncRNAs have longer size (over 200 nucleotides) and are involved in some key biological processes through various mechanisms. Involvement of miRNAs has been well documented in the development of PD, particularly gene expression. Hence, in this current review, we will discuss the impacts of miRNAs in regulation of the expression of PD-related genes and the role of lncRNAs in the pathogenesis of PD.


Noncoding RNA Parkinson’ disease MicroRNA Long non-coding RNA 


Compliance with ethical standards

Conflict of Interest

The authors have declared no conflicts of interest.


  1. 1.
    Wu Y, Le W, Jankovic J (2011) Preclinical biomarkers of Parkinson disease. Arch Neurol 68(1):22–30PubMedCrossRefGoogle Scholar
  2. 2.
    Zheng B et al (2010) PGC-1alpha, a potential therapeutic target for early intervention in Parkinson’s disease. Sci Transl Med . doi: 10.1126/scitranslmed.3001059 PubMedCentralGoogle Scholar
  3. 3.
    Papapetropoulos S, McCorquodale D (2007) Gene-expression profiling in Parkinson’s disease: discovery of valid biomarkers, molecular targets and biochemical pathways. Future Neurol 2:29–38CrossRefGoogle Scholar
  4. 4.
    Hamza TH et al (2010) Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson’s disease. Nat Genet 42(9):781–785PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Ibanez P et al (2004) Causal relation between α-synuclein locus duplication as a cause of familial Parkinson’s disease. Lancet 364(9440):1169–1171PubMedCrossRefGoogle Scholar
  6. 6.
    Chiba-Falek O, Lopez GJ, Nussbaum RL (2006) Levels of α-synuclein mRNA in sporadic Parkinson disease patients. Mov Disord 21(10):1703–1708PubMedCrossRefGoogle Scholar
  7. 7.
    Mandel S et al (2007) Applying transcriptomic and proteomic knowledge to Parkinson’s disease drug discovery. Exp Opin Drug Disc 2(9):1225–1240CrossRefGoogle Scholar
  8. 8.
    Grünblatt E (2012) Parkinson’s disease: molecular risk factors. Parkinsonism Relat Disord 18:S45–S48PubMedCrossRefGoogle Scholar
  9. 9.
    Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116(2):281–297PubMedCrossRefGoogle Scholar
  10. 10.
    Esteller M (2011) Non-coding RNAs in human disease. Nat Rev Genet 12(12):861–874PubMedCrossRefGoogle Scholar
  11. 11.
    Esquela-Kerscher A, Slack FJ (2006) Oncomirs—microRNAs with a role in cancer. Nat Rev Cancer 6(4):259–269PubMedCrossRefGoogle Scholar
  12. 12.
    Hammond SM (2005) MicroRNAs as tumor suppressors. Nat Genet 39(5):582–583CrossRefGoogle Scholar
  13. 13.
    Croce CM (2009) Causes and consequences of microRNA dysregulation in cancer. Nat Rev Genet 10(10):704–714PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Nicoloso MS et al (2009) MicroRNAs—the micro steering wheel of tumour metastases. Nat Rev Cancer 9(4):293–302PubMedCrossRefGoogle Scholar
  15. 15.
    Salta E, De Strooper B (2012) Non-coding RNAs with essential roles in neurodegenerative disorders. Lancet Neurol 11(2):189–200PubMedCrossRefGoogle Scholar
  16. 16.
    Ambros V (2001) microRNAs: tiny regulators with great potential. Cell 107(7):823–826PubMedCrossRefGoogle Scholar
  17. 17.
    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(5):843–854PubMedCrossRefGoogle Scholar
  18. 18.
    Vasudevan S, Tong Y, Steitz JA (2007) Switching from repression to activation: microRNAs can up-regulate translation. Science 318(5858):1931–1934PubMedCrossRefGoogle Scholar
  19. 19.
    Hu HY et al (2012) Evolution of the human-specific microRNA miR-941. Nature Commun 3:1145CrossRefGoogle Scholar
  20. 20.
    Robles AI, Harris CC (2013) A primate-specific microRNA enters the lung cancer landscape. Proc Natl Acad Sci 110(47):18748–18749PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Pauli A, Rinn JL, Schier AF (2011) Non-coding RNAs as regulators of embryogenesis. Nat Rev Genet 12(2):136–149PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Wang X et al (2011) The long arm of long noncoding RNAs: roles as sensors regulating gene transcriptional programs. Cold Spring Harb Perspect Biol 3:a003756PubMedPubMedCentralGoogle Scholar
  23. 23.
    Gupta RA et al (2010) Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature 464(7291):1071–1076PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Guttman M et al (2009) Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature 458(7235):223–227PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Pauli A et al (2012) Systematic identification of long noncoding RNAs expressed during zebrafish embryogenesis. Genome Res 22(3):577–591PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Li X et al (2013) Long noncoding RNAs: insights from biological features and functions to diseases. Med Res Rev 33(3):517–553PubMedCrossRefGoogle Scholar
  27. 27.
    Mercer TR, Dinger ME, Mattick JS (2009) Long non-coding RNAs: insights into functions. Nat Rev Genet 10(3):155–159PubMedCrossRefGoogle Scholar
  28. 28.
    Mercer TR et al (2008) Specific expression of long noncoding RNAs in the mouse brain. Proc Natl Acad Sci 105(2):716–721PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Ponting CP, Oliver PL, Reik W (2009) Evolution and functions of long noncoding RNAs. Cell 136(4):629–641PubMedCrossRefGoogle Scholar
  30. 30.
    Managadze D et al (2011) Negative correlation between expression level and evolutionary rate of long intergenic noncoding RNAs. Genome Biol Evol 3:1390–1404PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Melton C, Judson RL, Blelloch R (2010) Opposing microRNA families regulate self-renewal in mouse embryonic stem cells. Nature 463(7281):621–626PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136(2):215–233PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Ameres SL, Zamore PD (2013) Diversifying microRNA sequence and function. Nat Rev Mol Cell Biol 14(8):475–488PubMedCrossRefGoogle Scholar
  34. 34.
    Krol J, Loedige I, Filipowicz W (2010) The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet 11(9):597–610PubMedGoogle Scholar
  35. 35.
    Rüegger S, Großhans H (2012) MicroRNA turnover: when, how, and why. Trends Biochem Sci 37(10):436–446PubMedCrossRefGoogle Scholar
  36. 36.
    Westholm JO, Lai EC (2011) Mirtrons: microRNA biogenesis via splicing. Biochimie 93(11):1897–1904PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Fabian MR, Sonenberg N (2012) The mechanics of miRNA-mediated gene silencing: a look under the hood of miRISC. Nat Struct Mol Biol 19(6):586–593PubMedCrossRefGoogle Scholar
  38. 38.
    Gregory RI et al (2005) Human RISC couples microRNA biogenesis and posttranscriptional gene silencing. Cell 123(4):631–640PubMedCrossRefGoogle Scholar
  39. 39.
    Schwarz DS et al (2003) Asymmetry in the assembly of the RNAi enzyme complex. Cell 115(2):199–208PubMedCrossRefGoogle Scholar
  40. 40.
    Griffiths-Jones S (2004) The microRNA registry. Nucleic Acids Res 32(suppl 1):D109–D111PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Filipowicz W, Bhattacharyya SN, Sonenberg N (2008) Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nat Rev Genet 9(2):102–114PubMedCrossRefGoogle Scholar
  42. 42.
    Chen G et al (2013) LncRNADisease: a database for long-non-coding RNA-associated diseases. Nucleic Acids Res 41(D1):D983–D986PubMedCrossRefGoogle Scholar
  43. 43.
    Khalil AM et al (2009) Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc Natl Acad Sci 106(28):11667–11672PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Guttman M et al (2010) Ab initio reconstruction of cell type-specific transcriptomes in mouse reveals the conserved multi-exonic structure of lincRNAs. Nat Biotechnol 28(5):503–510PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Dinger ME et al (2008) Long noncoding RNAs in mouse embryonic stem cell pluripotency and differentiation. Genome Res 18(9):1433–1445PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Katayama S et al (2005) Antisense transcription in the mammalian transcriptome. Science 309(5740):1564–1566PubMedCrossRefGoogle Scholar
  47. 47.
    Faghihi MA, Wahlestedt C (2009) Regulatory roles of natural antisense transcripts. Nat Rev Mol Cell Biol 10(9):637–643PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    He Y et al (2008) The antisense transcriptomes of human cells. Science 322(5909):1855–1857PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Werner A, Sayer JA (2009) Naturally occurring antisense RNA: function and mechanisms of action. Curr Opin Nephrol Hypertens 18(4):343–349PubMedCrossRefGoogle Scholar
  50. 50.
    Rastinejad F, Blau HM (1993) Genetic complementation reveals a novel regulatory role for 3′ untranslated regions in growth and differentiation. Cell 72(6):903–917PubMedCrossRefGoogle Scholar
  51. 51.
    Sanchez-Herrero E, Akam M (1989) Spatially ordered transcription of regulatory DNA in the bithorax complex of Drosophila. Development 107(2):321–329PubMedGoogle Scholar
  52. 52.
    Heintzman ND et al (2007) Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome. Nat Genet 39(3):311–318PubMedCrossRefGoogle Scholar
  53. 53.
    Visel A et al (2009) ChIP-seq accurately predicts tissue-specific activity of enhancers. Nature 457(7231):854–858PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Kim T-K et al (2010) Widespread transcription at neuronal activity-regulated enhancers. Nature 465(7295):182–187PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Tisseur M, Kwapisz M, Morillon A (2011) Pervasive transcription–lessons from yeast. Biochimie 93(11):1889–1896PubMedCrossRefGoogle Scholar
  56. 56.
    Mattick JS (2010) Linc-ing long noncoding RNAs and enhancer function. Dev Cell 19(4):485–486PubMedCrossRefGoogle Scholar
  57. 57.
    Jalali S et al (2013) Systematic transcriptome wide analysis of lncRNA–miRNA interactions. PLoS One 8(2):e53823PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Ouellet DL et al. (2006) MicroRNAs in gene regulation: when the smallest governs it all. BioMed Research InternationalGoogle Scholar
  59. 59.
    Friedman RC et al (2009) Most mammalian mRNAs are conserved targets of microRNAs. Genome Res 19(1):92–105PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Lewis BP, Burge CB, Bartel DP (2005) Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. cell 120(1):15–20PubMedCrossRefGoogle Scholar
  61. 61.
    Hutvágner G, Zamore PD (2002) A microRNA in a multiple-turnover RNAi enzyme complex. Science 297(5589):2056–2060PubMedCrossRefGoogle Scholar
  62. 62.
    Zeng Y, Cullen BR (2003) Sequence requirements for micro RNA processing and function in human cells. RNA 9(1):112–123PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Zeng Y, Wagner EJ, Cullen BR (2002) Both natural and designed micro RNAs can inhibit the expression of cognate mRNAs when expressed in human cells. Mol Cell 9(6):1327–1333PubMedCrossRefGoogle Scholar
  64. 64.
    Doench JG, Petersen CP, Sharp PA (2003) siRNAs can function as miRNAs. Genes Dev 17(4):438–442PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Seggerson K, Tang L, Moss EG (2002) Two genetic circuits repress the Caenorhabditis elegans heterochronic gene lin-28 after translation initiation. Developmental biology 243(2):215–225PubMedCrossRefGoogle Scholar
  66. 66.
    Brennecke J et al (2003) Bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila. Cell 113(1):25–36PubMedCrossRefGoogle Scholar
  67. 67.
    Wapinski O, Chang HY (2011) Long noncoding RNAs and human disease. Trends Cell Biol 21(6):354–361PubMedCrossRefGoogle Scholar
  68. 68.
    Bernstein E, Allis CD (2005) RNA meets chromatin. Genes Dev 19(14):1635–1655PubMedCrossRefGoogle Scholar
  69. 69.
    Whitehead J, Pandey GK, Kanduri C (2009) Regulation of the mammalian epigenome by long noncoding RNAs. Biochimica et Biophysica Acta 1790(9):936–947PubMedCrossRefGoogle Scholar
  70. 70.
    Bracken AP, Helin K (2009) Polycomb group proteins: navigators of lineage pathways led astray in cancer. Nat Rev Cancer 9(11):773–784PubMedCrossRefGoogle Scholar
  71. 71.
    Guenther MG et al (2007) A chromatin landmark and transcription initiation at most promoters in human cells. Cell 130(1):77–88PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Bonasio R, Tu S, Reinberg D (2010) Molecular signals of epigenetic states. Science 330(6004):612–616PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Hung T, Chang HY (2010) Long noncoding RNA in genome regulation: prospects and mechanisms. RNA Biol 7(5):582–585PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Lee JT (2009) Lessons from X-chromosome inactivation: long ncRNA as guides and tethers to the epigenome. Genes Dev 23(16):1831–1842PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Spitale RC, Tsai M-C, Chang HY (2011) RNA templating the epigenome: long noncoding RNAs as molecular scaffolds. Epigenetics 6(5):539–543PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Good MC, Zalatan JG, Lim WA (2011) Scaffold proteins: hubs for controlling the flow of cellular information. Science 332(6030):680–686PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Cheng L-C, Tavazoie M, Doetsch F (2005) Stem cells: from epigeneticsto microRNAs. Neuron 46(3):363–367PubMedCrossRefGoogle Scholar
  78. 78.
    Jin P, Alisch RS, Warren ST (2004) RNA and microRNAs in fragile X mental retardation. Nat Cell Biol 6(11):1048–1053PubMedCrossRefGoogle Scholar
  79. 79.
    Schratt GM et al (2006) A brain-specific microRNA regulates dendritic spine development. Nature 439(7074):283–289PubMedCrossRefGoogle Scholar
  80. 80.
    Sempere LF et al (2004) Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation. Genome Biol 5(3):R13PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Smirnova L et al (2005) Regulation of miRNA expression during neural cell specification. Eur J Neurosci 21(6):1469–1477PubMedCrossRefGoogle Scholar
  82. 82.
    Kosik KS, Krichevsky AM (2005) The elegance of the microRNAs: a neuronal perspective. Neuron 47(6):779–782PubMedCrossRefGoogle Scholar
  83. 83.
    Krichevsky AM et al (2003) A microRNA array reveals extensive regulation of microRNAs during brain development. RNA 9(10):1274–1281PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Chen W, Qin C (2015) General hallmarks of microRNAs in brain evolution and development. RNA Biol 12(7):701–708PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Lopez JP et al (2014) miR-1202: a primate specific and brain enriched mirna involved in major depression and antidepressant treatment. Nat Med 20(7):764PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    John B et al (2004) Human microRNA targets. PLoS Biol 2(11):e363PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Kim J et al (2004) Identification of many microRNAs that copurify with polyribosomes in mammalian neurons. Proc Natl Acad Sci 101(1):360–365PubMedCrossRefGoogle Scholar
  88. 88.
    Martin KC, Kosik KS (2002) Synaptic tagging—who’s it? Nat Rev Neurosci 3(10):813–820PubMedCrossRefGoogle Scholar
  89. 89.
    Schaeffer C et al (2003) The RNA binding protein FMRP: new connections and missing links. Biol Cell 95(3–4):221–228PubMedCrossRefGoogle Scholar
  90. 90.
    Lugli G et al (2005) Dicer and eIF2c are enriched at postsynaptic densities in adult mouse brain and are modified by neuronal activity in a calpain-dependent manner. J Neurochem 94(4):896–905PubMedCrossRefGoogle Scholar
  91. 91.
    Ashraf SI et al (2006) Synaptic protein synthesis associated with memory is regulated by the RISC pathway in Drosophila. Cell 124(1):191–205PubMedCrossRefGoogle Scholar
  92. 92.
    Mehler MF, Mattick JS (2007) Noncoding RNAs and RNA editing in brain development, functional diversification, and neurological disease. Physiol Rev 87(3):799–823PubMedCrossRefGoogle Scholar
  93. 93.
    Qureshi IA, Mattick JS, Mehler MF (2010) Long non-coding RNAs in nervous system function and disease. Brain Res 1338:20–35PubMedCrossRefGoogle Scholar
  94. 94.
    Dauer W, Przedborski S (2003) Parkinson’s disease: mechanisms and models. Neuron 39(6):889–909PubMedCrossRefGoogle Scholar
  95. 95.
    Marsden C (1982) Neuromelanin and Parkinson’s disease. J Neural Transm Suppl 19:121–141Google Scholar
  96. 96.
    Wu D-C et al (2003) NADPH oxidase mediates oxidative stress in the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine model of Parkinson’s disease. Proc Natl Acad Sci 100(10):6145–6150PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Uhl GR (1998) Hypothesis: the role of dopaminergic transporters in selective vulnerability of cells in Parkinson’s disease. Ann Neurol 43(5):555–560PubMedCrossRefGoogle Scholar
  98. 98.
    Damier P et al (1993) Glutathione peroxidase, glial cells and Parkinson’s disease. Neuroscience 52(1):1–6PubMedCrossRefGoogle Scholar
  99. 99.
    Dexter D et al (1989) Increased nigral iron content and alterations in other metal ions occurring in brain in Parkinson’s disease. J Neurochem 52(6):1830–1836PubMedCrossRefGoogle Scholar
  100. 100.
    Riederer P et al (1989) Transition metals, ferritin, glutathione, and ascorbic acid in parkinsonian brains. J Neurochem 52(2):515–520PubMedCrossRefGoogle Scholar
  101. 101.
    Sofic E et al (1992) Reduced and oxidized glutathione in the substantia nigra of patients with Parkinson’s disease. Neurosci Lett 142(2):128–130PubMedCrossRefGoogle Scholar
  102. 102.
    Blum D et al (2001) Molecular pathways involved in the neurotoxicity of 6-OHDA, dopamine and MPTP: contribution to the apoptotic theory in Parkinson’s disease. Prog Neurobiol 65(2):135–172PubMedCrossRefGoogle Scholar
  103. 103.
    Klein C, Westenberger A (2012) Genetics of Parkinson’s disease. Cold Spring Harb Perspect Medicin 2(1):a008888Google Scholar
  104. 104.
    Farrer M et al (2004) Comparison of kindreds with parkinsonism and α-synuclein genomic multiplications. Ann Neurol 55(2):174–179PubMedCrossRefGoogle Scholar
  105. 105.
    Singleton A et al (2003) α-Synuclein locus triplication causes Parkinson’s disease. Science 302(5646):841PubMedCrossRefGoogle Scholar
  106. 106.
    West AB et al (2005) Parkinson’s disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity. Proc Natl Acad Sci USA 102(46):16842–16847PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Brice A (2005) Genetics of Parkinson’s disease: lRRK2 on the rise. Brain 128(12):2760–2762PubMedCrossRefGoogle Scholar
  108. 108.
    Heman-Ackah SM et al (2013) RISC in PD: the impact of microRNAs in Parkinson’s disease cellular and molecular pathogenesis. Frontiers in molecular neuroscience. doi: 10.3389/fnmol.2013.00040 PubMedPubMedCentralGoogle Scholar
  109. 109.
    Lev N et al (2006) Role of DJ-1 in Parkinson’s disease. J Mol Neurosci 29(3):215–225PubMedCrossRefGoogle Scholar
  110. 110.
    Mizuno Y et al (2001) Parkin and Parkinson’s disease. Curr Opin Neurol 14(4):477–482PubMedCrossRefGoogle Scholar
  111. 111.
    Dawson TM, Dawson VL (2010) The role of parkin in familial and sporadic Parkinson’s disease. Mov Disord 25(S1):S32–S39PubMedPubMedCentralCrossRefGoogle Scholar
  112. 112.
    Jones R (2010) The roles of PINK1 and Parkin in Parkinson’s disease. PLoS Biol 8(1):e1000299PubMedPubMedCentralCrossRefGoogle Scholar
  113. 113.
    Gandhi S et al (2006) PINK1 protein in normal human brain and Parkinson’s disease. Brain 129(7):1720–1731PubMedCrossRefGoogle Scholar
  114. 114.
    Dehay B et al (2012) Lysosomal dysfunction in Parkinson disease: aTP13A2 gets into the groove. Autophagy 8(9):1389–1391PubMedPubMedCentralCrossRefGoogle Scholar
  115. 115.
    Park JS. et al (2014) Parkinson’s disease-associated human ATP13A2 (PARK9) deficiency causes zinc dyshomeostasis and mitochondrial dysfunction. Human mole genet p ddt623Google Scholar
  116. 116.
    Kim J et al (2007) A MicroRNA feedback circuit in midbrain dopamine neurons. Science 317(5842):1220–1224PubMedPubMedCentralCrossRefGoogle Scholar
  117. 117.
    Doxakis E (2010) Post-transcriptional regulation of α-synuclein expression by mir-7 and mir-153. J Biol Chem 285(17):12726–12734PubMedPubMedCentralCrossRefGoogle Scholar
  118. 118.
    Junn E et al (2009) Repression of α-synuclein expression and toxicity by microRNA-7. Proc Natl Acad Sci 106(31):13052–13057PubMedPubMedCentralCrossRefGoogle Scholar
  119. 119.
    Wang G et al (2008) Variation in the miRNA-433 binding site of FGF20 confers risk for Parkinson disease by overexpression of α-synuclein. Am J Hum Genet 82(2):283–289PubMedPubMedCentralCrossRefGoogle Scholar
  120. 120.
    Margis R, Margis R, Rieder CR (2011) Identification of blood microRNAs associated to Parkinsońs disease. J Biotechnol 152(3):96–101PubMedCrossRefGoogle Scholar
  121. 121.
    Valadi H et al (2007) Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 9(6):654–659PubMedCrossRefGoogle Scholar
  122. 122.
    Cardo LF et al (2013) Profile of microRNAs in the plasma of Parkinson’s disease patients and healthy controls. J Neurol 260(5):1420PubMedCrossRefGoogle Scholar
  123. 123.
    Soreq L et al (2013) Small RNA sequencing-microarray analyses in Parkinson leukocytes reveal deep brain stimulation-induced splicing changes that classify brain region transcriptomes. Front Mol Neurosci 6:10PubMedPubMedCentralCrossRefGoogle Scholar
  124. 124.
    Khoo SK et al (2012) Plasma-based circulating MicroRNA biomarkers for Parkinson’s disease. J Parkinson’s Dis 2(4):321–331Google Scholar
  125. 125.
    Gehrke S et al (2010) Pathogenic LRRK2 negatively regulates microRNA-mediated translational repression. Nature 466(7306):637–641PubMedPubMedCentralCrossRefGoogle Scholar
  126. 126.
    Cho HJ et al (2013) MicroRNA-205 regulates the expression of Parkinson’s disease-related leucine-rich repeat kinase 2 protein. Hum Mol Genet 22(3):608–620PubMedCrossRefGoogle Scholar
  127. 127.
    Shaked I et al (2009) MicroRNA-132 potentiates cholinergic anti-inflammatory signaling by targeting acetylcholinesterase. Immunity 31(6):965–973PubMedCrossRefGoogle Scholar
  128. 128.
    Yang D et al (2012) miR-132 regulates the differentiation of dopamine neurons by directly targeting Nurr1 expression. J Cell Sci 125(7):1673–1682PubMedCrossRefGoogle Scholar
  129. 129.
    Soreq H (2015) MicroRNA-target interactions in neurodegenerative diseases. SpringerPlus 4(Suppl 1):L1PubMedGoogle Scholar
  130. 130.
    Kanagaraj N et al (2014) Downregulation of miR-124 in MPTP-treated mouse model of Parkinson’s disease and MPP iodide-treated MN9D cells modulates the expression of the calpain/cdk5 pathway proteins. Neuroscience 272:167–179PubMedCrossRefGoogle Scholar
  131. 131.
    Gong X et al (2016) miR-124 regulates cell apoptosis and autophagy in dopaminergic neurons and protects them by regulating AMPK/mTOR pathway in Parkinson’s disease. Am J Transl Res 8(5):2127–2137PubMedPubMedCentralGoogle Scholar
  132. 132.
    Kim J et al (2015) MicroRNA-124 regulates glucocorticoid sensitivity by targeting phosphodiesterase 4B in diffuse large B cell lymphoma. Gene 558(1):173–180PubMedCrossRefGoogle Scholar
  133. 133.
    Ledderose C et al (2012) Corticosteroid resistance in sepsis is influenced by microRNA-124–induced downregulation of glucocorticoid receptor-α*. Crit Care Med 40(10):2745–2753PubMedCrossRefGoogle Scholar
  134. 134.
    Herrero, M.-T., et al., Inflammation in Parkinson’s disease: role of glucocorticoids. Front Neuroanat 2015. 9 Google Scholar
  135. 135.
    Miñones-Moyano E et al (2011) MicroRNA profiling of Parkinson’s disease brains identifies early downregulation of miR-34b/c which modulate mitochondrial function. Hum Mol Genet 20(15):3067–3078PubMedCrossRefGoogle Scholar
  136. 136.
    Soreq L et al (2014) Long non-coding RNA and alternative splicing modulations in Parkinson’s leukocytes identified by RNA sequencing. PLoS Comput Biol 10(3):e1003517PubMedPubMedCentralCrossRefGoogle Scholar
  137. 137.
    Carrieri C et al (2015) Expression analysis of the long non-coding RNA antisense to Uchl1 (AS Uchl1) during dopaminergic cells’ differentiation in vitro and in neurochemical models of Parkinson’s disease. Front Cellular Neurosci 9:114CrossRefGoogle Scholar
  138. 138.
    Matsui M, Corey DR (2016) Non-coding RNAs as drug targets. Nat Rev Drug Discov. doi: 10.1038/nrd.2016.117 PubMedGoogle Scholar
  139. 139.
    Bennett CF, Swayze EE (2010) RNA targeting therapeutics: molecular mechanisms ofAntisense oligonucleotides as a therapeutic platform. Annu Rev Pharmacol Toxicol 50:259–293PubMedCrossRefGoogle Scholar
  140. 140.
    Chen X (2015) Predicting lncRNA-disease associations and constructing lncRNA functional similarity network based on the information of miRNA. Sci Rep 17(5):13186CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2016

Authors and Affiliations

  • Maryam Majidinia
    • 1
  • Aynaz Mihanfar
    • 1
  • Reza Rahbarghazi
    • 2
  • Alireza Nourazarian
    • 1
    • 2
    • 3
  • BakiyeGoker Bagca
    • 4
  • Çığır Biray Avci
    • 4
  1. 1.Department of Biochemistry and Clinical Laboratories, Faculty of MedicineTabriz University of Medical SciencesTabrizIran
  2. 2.Stem Cell Research CenterTabriz University of Medical SciencesTabrizIran
  3. 3.Research Center for Pharmaceutical NanotechnologyTabriz University of Medical SciencesTabrizIran
  4. 4.Department of Medical Biology, Faculty of MedicineEge UniversityIzmirTurkey

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