The role of the protein–RNA recognition code in neurodegeneration

  • Jozef NahalkaEmail author


MicroRNAs are small endogenous RNAs that pair and bind to sites on mRNAs to direct post-transcriptional repression. However, there is a possibility that microRNAs directly influence protein structure and activity, and this influence can be termed post-translational riboregulation. This conceptual review explores the literature on neurodegenerative disorders. Research on the association between neurodegeneration and RNA-repeat toxicity provides data that support a protein–RNA recognition code. For example, this code explains why hnRNP H and SFPQ proteins, which are involved in amyotrophic lateral sclerosis, are sequestered by the (GGGGCC)n repeat sequence. Similarly, it explains why MNBL proteins and (CTG)n repeats in RNA, which are involved in myotonic dystrophy, are sequestered into RNA foci. Using this code, proteins involved in diseases can be identified. A simple protein BLAST search of the human genome for amino acid repeats that correspond to the nucleotide repeats reveals new proteins among already known proteins that are involved in diseases. For example, the (CAG)n repeat sequence, when transcribed into possible peptide sequences, leads to the identification of PTCD3, Rem2, MESP2, SYPL2, WDR33, COL23A1, and others. After confirming this approach on RNA repeats, in the next step, the code was used in the opposite manner. Proteins that are involved in diseases were compared with microRNAs involved in those diseases. For example, a reasonable correspondence of microRNA 9 and 107 with amyloid-β-peptide (Aβ42) was identified. In the last step, a miRBase search for micro-nucleotides, obtained by transcription of a prion amino acid sequence, revealed new microRNAs and microRNAs that have previously been identified as involved in prion diseases. This concept provides a useful key for designing RNA or peptide probes.


Molecular recognition Non-coding RNA Huntington’s disease Alzheimer’s disease Parkinson’s disease Prion diseases 



This work was supported by “Vedecká grantová agentúra MŠVVaŠ SR a SAV” (VEGA 2/0058/17) and the Research and Development Operational Programme (ITMS 26220120054).


  1. 1.
    Beadle GW, Tatum EL (1941) Genetic control of biochemical reactions in Neurospora. Genetics 27:499–506Google Scholar
  2. 2.
    Gerstein MB, Bruce C, Rozowsky JS, Zheng D, Du J, Korbel JO, Emanuelsson O, Zhang ZD, Weissman S, Snyder M (2007) What is a gene, post-ENCODE? History and updated definition. Genome Res 17:669–681CrossRefPubMedGoogle Scholar
  3. 3.
    Dunham I, Kundaje A, Aldred SF, Collins PJ, Davis CA, Doyle F, Epstein CB, Frietze S, Harrow J, Kaul R, Khatun J, Lajoie BR, Landt SG, Lee B-, Pauli F, Rosenbloom KR et al (2012) An integrated encyclopedia of DNA elements in the human genome. Nature 489:57–74CrossRefGoogle Scholar
  4. 4.
    Felsenfeld G (2014) A brief history of epigenetics. Cold Spring Harbor Perspect Biol 6:a018200CrossRefGoogle Scholar
  5. 5.
    Yao B, Christian KM, He C, Jin P, Ming G-, Song H (2016) Epigenetic mechanisms in neurogenesis. Nat Rev Neurosci 17:537–549CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Maison C, Bailly D, Peters AHFM, Quivy J-, Roche D, Taddei A, Lachner M, Jenuwein T, Almouzni G (2002) Higher-order structure in pericentric heterochromatin involves a distinct pattern of histone modification and an RNA component. Nat Genet 30:329–334CrossRefPubMedGoogle Scholar
  7. 7.
    Chen J, Xue Y (2016) Emerging roles of non-coding RNAs in epigenetic regulation. Sci China Life Sci 59:227–235CrossRefPubMedGoogle Scholar
  8. 8.
    Salta E, De Strooper B (2017) Noncoding RNAs in neurodegeneration. Nat Rev Neurosci 18:627–640CrossRefPubMedGoogle Scholar
  9. 9.
    Gebert LFR, MacRae IJ (2019) Regulation of microRNA function in animals. Nat Rev Mol Cell Biol 20:21–37CrossRefPubMedGoogle Scholar
  10. 10.
    Swarts DC, Makarova K, Wang Y, Nakanishi K, Ketting RF, Koonin EV, Patel DJ, Van Der Oost J (2014) The evolutionary journey of argonaute proteins. Nat Struct Mol Biol 21:743–753CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Friedman RC, Farh KK-, Burge CB, Bartel DP (2009) Most mammalian mRNAs are conserved targets of microRNAs. Genome Res 19:92–105CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Kozomara A, Griffiths-Jones S (2014) MiRBase: annotating high confidence microRNAs using deep sequencing data. Nucleic Acids Res 42:D68–D73CrossRefPubMedGoogle Scholar
  13. 13.
    Tsang J, Zhu J, van Oudenaarden A (2007) MicroRNA-mediated feedback and feedforward loops are recurrent network motifs in mammals. Mol Cell 26:753–767CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Ebert MS, Sharp PA (2012) Roles for microRNAs in conferring robustness to biological processes. Cell 149:505–524CrossRefGoogle Scholar
  15. 15.
    Villarroya-Beltri C, Baixauli F, Gutiérrez-Vázquez C, Sánchez-Madrid F, Mittelbrunn M (2014) Sorting it out: regulation of exosome loading. Semin Cancer Biol 28:3–13CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Derrien T, Johnson R, Bussotti G, Tanzer A, Djebali S, Tilgner H, Guernec G, Martin D, Merkel A, Knowles DG, Lagarde J, Veeravalli L, Ruan X, Ruan Y, Lassmann T, Carninci P, Brown JB, Lipovich L, Gonzalez JM, Thomas M, Davis CA, Shiekhattar R, Gingeras TR, Hubbard TJ, Notredame C, Harrow J, Guigó R (2012) The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression. Genome Res 22:1775–1789CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Uszczynska-Ratajczak B, Lagarde J, Frankish A, Guigó R, Johnson R (2018) Towards a complete map of the human long non-coding RNA transcriptome. Nat Rev Gen 19:535–548CrossRefGoogle Scholar
  18. 18.
    Munschauer M, Nguyen CT, Sirokman K, Hartigan CR, Hogstrom L, Engreitz JM, Ulirsch JC, Fulco CP, Subramanian V, Chen J, Schenone M, Guttman M, Carr SA, Lander ES (2018) The NORAD lncRNA assembles a topoisomerase complex critical for genome stability. Nature 561:132–136CrossRefPubMedGoogle Scholar
  19. 19.
    Holley RW, Apgar J, Everett GA, Madison JT, Marquisee M, Merrill SH, Penswick JR, Zamir A (1965) Structure of a ribonucleic acid. Science 147:1462–1465CrossRefPubMedGoogle Scholar
  20. 20.
    Engreitz JM, Sirokman K, McDonel P, Shishkin AA, Surka C, Russell P, Grossman SR, Chow AY, Guttman M, Lander ES (2014) RNA-RNA interactions enable specific targeting of noncoding RNAs to nascent pre-mRNAs and chromatin sites. Cell 159:188–199CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Barry G (2014) Integrating the roles of long and small non-coding RNA in brain function and disease. Mol Psychiatry 19:410–416CrossRefPubMedGoogle Scholar
  22. 22.
    Hentze MW, Castello A, Schwarzl T, Preiss T (2018) A brave new world of RNA-binding proteins. Nat Rev Mol Cell Biol 19:327–341CrossRefPubMedGoogle Scholar
  23. 23.
    Wahl MC, Will CL, Lührmann R (2009) The spliceosome: design principles of a dynamic RNP machine. Cell 136:701–718CrossRefPubMedGoogle Scholar
  24. 24.
    Basu S, Bahadur RP (2016) A structural perspective of RNA recognition by intrinsically disordered proteins. Cell Mol Life Sci 73:4075–4084CrossRefPubMedGoogle Scholar
  25. 25.
    Castello A, Fischer B, Frese CK, Horos R, Alleaume A-, Foehr S, Curk T, Krijgsveld J, Hentze MW (2016) Comprehensive identification of RNA-binding domains in human cells. Mol Cell 63:696–710CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Mackowiak SD, Zauber H, Bielow C, Thiel D, Kutz K, Calviello L, Mastrobuoni G, Rajewsky N, Kempa S, Selbach M, Obermayer B (2015) Extensive identification and analysis of conserved small ORFs in animals. Genome Biol 16:179CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Nahalka J (2014) Protein-RNA recognition: cracking the code. J Theor Biol 343:9–15CrossRefPubMedGoogle Scholar
  28. 28.
    Nahalka J (2011) Quantification of peptide bond types in human proteome indicates how DNA codons were assembled at prebiotic conditions. J Proteom Bioinform 4:153–159CrossRefGoogle Scholar
  29. 29.
    Li Y, McGrail DJ, Xu J, Li J, Liu NN, Sun M, Lin R, Pancsa R, Zhang J, Lee JS, Wang H, Mills GB, Li X, Yi S, Sahni N (2018) MERIT: systematic analysis and characterization of mutational effect on RNA interactome topology. Hepatology. CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Tang Y, Zhou T, Yu X, Xue Z, Shen N (2017) The role of long non-coding RNAs in rheumatic diseases. Nat Rev Rheumatol 13:657–669CrossRefPubMedGoogle Scholar
  31. 31.
    Todd TW, Petrucelli L (2018) Neurodegenerative diseases and RNA-mediated toxicity. In: Wolfe MS (ed) The molecular and cellular basis of neurodegenerative diseases: underlying mechanisms, 1st edn. Academic Press, New York, pp 441–475CrossRefGoogle Scholar
  32. 32.
    Katsnelson A, De Strooper B, Zoghbi HY (2016) Neurodegeneration: from cellular concepts to clinical applications. Sci Transl Med 8:364CrossRefGoogle Scholar
  33. 33.
    Zhang N, Ashizawa T (2017) RNA toxicity and foci formation in microsatellite expansion diseases. Curr Opin Genet Dev 44:17–29CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Zu T, Gibbens B, Doty NS, Gomes-Pereira M, Huguet A, Stone MD, Margolis J, Peterson M, Markowski TW, Ingram MAC, Nan Z, Forster C, Low WC, Schoser B, Somia NV, Clark HB, Schmechel S, Bitterman PB, Gourdon G, Swanson MS, Moseley M, Ranum LPW (2011) Non-ATG-initiated translation directed by microsatellite expansions. Proc Natl Acad Sci USA 108:260–265CrossRefPubMedGoogle Scholar
  35. 35.
    Hardiman O, Al-Chalabi A, Chio A, Corr EM, Logroscino G, Robberecht W, Shaw PJ, Simmons Z, Van Den Berg LH (2017) Amyotrophic lateral sclerosis. Nat Rev Disease Prim 3:17071CrossRefGoogle Scholar
  36. 36.
    Haeusler AR, Donnelly CJ, Rothstein JD (2016) The expanding biology of the C9orf72 nucleotide repeat expansion in neurodegenerative disease. Nat Rev Neurosci 17:383–395CrossRefPubMedGoogle Scholar
  37. 37.
    Paronetto MP (2013) Ewing sarcoma protein: a key player in human cancer. Int J Cell Biol 2013:642853CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Couthouis J, Hart MP, Erion R, King OD, Diaz Z, Nakaya T, Ibrahim F, Kim H-, Mojsilovic-petrovic J, Panossian S, Kim CE, Frackelton EC, Solski JA, Williams KL, Clay-falcone D, Elman L, McCluskey L, Greene R, Hakonarson H, Kalb RG, Lee VMY, Trojanowski JQ, Nicholson GA, Blair IP, Bonini NM, Van Deerlin VM, Mourelatos Z, Shorter J, Gitler AD (2012) Evaluating the role of the FUS/TLS-related gene EWSR1 in amyotrophic lateral sclerosis. Hum Mol Genet 21:2899–2911CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Barmada SJ, Ju S, Arjun A, Batarse A, Archbold HC, Peisach D, Li X, Zhang Y, Tank EMH, Qiu H, Huang EJ, Ringe D, Petsko GA, Finkbeiner S (2015) Amelioration of toxicity in neuronal models of amyotrophic lateral sclerosis by hUPF1. Proc Natl Acad Sci USA 112:7821–7826CrossRefPubMedGoogle Scholar
  40. 40.
    Kim Y-, Watanabe T, Allen PB, Kim Y-, Lee S-, Greengard P, Nairn AC, Kwon Y- (2003) PNUTS, a protein phosphatase 1 (PP1) NUclear targeting subunit: characterization of its PP1 and RNA-binding domains and regulation by phosphorylation. J Biol Chem 278:13819–13828CrossRefPubMedGoogle Scholar
  41. 41.
    Meola G, Cardani R (2015) Myotonic dystrophies: an update on clinical aspects, genetic, pathology, and molecular pathomechanisms. Biochim Biophys Acta Mol Basis Dis 1852:594–606CrossRefGoogle Scholar
  42. 42.
    Timchenko LT, Miller JW, Timchenko NA, Devore DR, Datar KV, Lin L, Roberts R, Thomas Caskey C, Swanson MS (1996) Identification of a (CUG)(n) triplet repeat RNA-binding protein and its expression in myotonic dystrophy. Nucleic Acids Res 24:4407–4414CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Ho TH, Bundman D, Armstrong DL, Cooper TA (2005) Transgenic mice expressing CUG-BP1 reproduce splicing mis-regulation observed in myotonic dystrophy. Hum Mol Genet 14:1539–1547CrossRefPubMedGoogle Scholar
  44. 44.
    Wan Q, Schuchman EH (1995) A novel polymorphism in the human acid sphingomyelinase gene due to size variation of the signal peptide region. Biochim Biophys Acta Mol Basis Dis 1270:207–210CrossRefGoogle Scholar
  45. 45.
    Bodmer D, Eleveld M, Kater-Baats E, Janssen I, Janssen B, Weterman M, Schoenmakers E, Nickerson M, Linehan M, Zbar B, Van Kessel AG (2002) Disruption of a novel MFS transporter gene, DIRC2, by a familial renal cell carcinoma-associated t(2;3)(q35;q21). Hum Mol Genet 11:641–649CrossRefPubMedGoogle Scholar
  46. 46.
    Addeo A, Bini R, Viora T, Bonaccorsi L, Leli R (2013) Von hippel-lindau and myotonic dystrophy of steinert along with pancreatic neuroendocrine tumor and renal clear cell carcinomal neoplasm: case report and review of the literature. Int J Surg Case Rep 4:648–650CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Ross CA, Tabrizi SJ (2011) Huntington’s disease: from molecular pathogenesis to clinical treatment. Lancet Neurol 10:83–98CrossRefPubMedGoogle Scholar
  48. 48.
    Gomez-Pastor R, Burchfiel ET, Neef DW, Jaeger AM, Cabiscol E, McKinstry SU, Doss A, Aballay A, Lo DC, Akimov SS, Ross CA, Eroglu C, Thiele DJ (2017) Abnormal degradation of the neuronal stress-protective transcription factor HSF1 in huntington’s disease. Nat Commun 8:14405CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Davies SMK, Rackham O, Shearwood A-J, Hamilton KL, Narsai R, Whelan J, Filipovska A (2009) Pentatricopeptide repeat domain protein 3 associates with the mitochondrial small ribosomal subunit and regulates translation. FEBS Lett 583:1853–1858CrossRefPubMedGoogle Scholar
  50. 50.
    Quintanilla RA, Johnson GVW (2009) Role of mitochondrial dysfunction in the pathogenesis of huntington’s disease. Brain Res Bull 80:242–247CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Krol J, Fiszer A, Mykowska A, Sobczak K, de Mezer M, Krzyzosiak WJ (2007) Ribonuclease dicer cleaves triplet repeat hairpins into shorter repeats that silence specific targets. Mol Cell 25:575–586CrossRefPubMedGoogle Scholar
  52. 52.
    Edel MJ, Boué S, Menchon C, Sánchez-Danés A, Belmonte JCI (2010) Rem2 GTPase controls proliferation and apoptosis of neurons during embryo development. Cell Cycle 9:3414–3422CrossRefPubMedGoogle Scholar
  53. 53.
    Paradis S, Harrar DB, Lin Y, Koon AC, Hauser JL, Griffith EC, Zhu L, Brass LF, Chen C, Greenberg ME (2007) An RNAi-based approach identifies molecules required for glutamatergic and GABAergic synapse development. Neuron 53:217–232CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Andersson ER, Lendahl U (2014) Therapeutic modulation of notch signalling-are we there yet? Nat Rev Drug Discov 13:357–378CrossRefPubMedGoogle Scholar
  55. 55.
    Whittock NV, Sparrow DB, Wouters MA, Sillence D, Ellard S, Dunwoodie SL, Turnpenny PD (2004) Mutated/MESP2 causes spondylocostal dysostosis in humans. Am J Hum Genet 74:1249–1254CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Bonini SA, Ferrari Toninelli G, Montinaro M, Memo M (2013) Notch signalling in adult neurons: a potential target for microtubule stabilization. Ther Adv Neurol Disord 6:375–385CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Trushina E, Heldebrant MP, Perez-Terzic CM, Bortolon R, Kovtun IV, Badger JD II, Terzic A, Estévez A, Windebank AJ, Dyer RB, Yao J, McMurray CT (2003) Microtubule destabilization and nuclear entry are sequential steps leading to toxicity in huntington’s disease. Proc Natl Acad Sci USA 100:12171–12176CrossRefPubMedGoogle Scholar
  58. 58.
    Chang DTW, Rintoul GL, Pandipati S, Reynolds IJ (2006) Mutant huntingtin aggregates impair mitochondrial movement and trafficking in cortical neurons. Neurobiol Dis 22:388–400CrossRefPubMedGoogle Scholar
  59. 59.
    Chen S, Lu FF, Seeman P, Liu F (2012) Quantitative proteomic analysis of human substantia nigra in alzheimer’s disease, huntington’s disease and multiple sclerosis. Neurochem Res 37:2805–2813CrossRefPubMedGoogle Scholar
  60. 60.
    Goto S, Hirano A (1990) Synaptophysin expression in the striatum in huntington’s disease. Acta Neuropathol 80:88–91CrossRefPubMedGoogle Scholar
  61. 61.
    Clerici M, Faini M, Aebersold R, Jinek M (2017) Structural insights into the assembly and polya signal recognition mechanism of the human CPSF complex. ELife 6:e33111CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Clerici M, Faini M, Muckenfuss LM, Aebersold R, Jinek M (2018) Structural basis of AAUAAA polyadenylation signal recognition by the human CPSF complex. Nat Struct Mol Biol 25:135–138CrossRefPubMedGoogle Scholar
  63. 63.
    Romo L, Ashar-Patel A, Pfister E, Aronin N (2017) Alterations in mRNA 3′ UTR isoform abundance accompany gene expression changes in human huntington’s disease brains. Cell Rep 20:3057–3070CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Monavarfeshani A, Knill CN, Sabbagh U, Su J, Fox MA (2017) Region- and cell-specific expression of transmembrane collagens in mouse brain. Front Integr Neurosci 11:20CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Walker FO (2007) Huntington’s disease. Lancet 369:218–228CrossRefPubMedGoogle Scholar
  66. 66.
    Xiong A, Wesson DW (2016) Illustrated review of the ventral striatum’s olfactory tubercle. Chem Senses 41:549–555PubMedPubMedCentralGoogle Scholar
  67. 67.
    Spivey KA, Chung I, Banyard J, Adini I, Feldman HA, Zetter BR (2012) A role for collagen XXIII in cancer cell adhesion, anchorage-independence and metastasis. Oncogene 31:2362–2372CrossRefPubMedGoogle Scholar
  68. 68.
    Sørensen SA, Fenger K, Olsen JH (1999) Significantly lower incidence of cancer among patients with huntington disease: an apoptotic effect of an expanded polyglutamine tract? Cancer 86:1342–1346CrossRefPubMedGoogle Scholar
  69. 69.
    Murmann AE, Gao QQ, Putzbach WE, Patel M, Bartom ET, Law CY, Bridgeman B, Chen S, McMahon KM, Thaxton CS, Peter ME (2018) Small interfering RNAs based on huntingtin trinucleotide repeats are highly toxic to cancer cells. EMBO Rep 19:e45336CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Cescon M, Chen P, Castagnaro S, Gregorio I, Bonaldo P (2016) Lack of collagen VI promotes neurodegeneration by impairing autophagy and inducing apoptosis during aging. Aging 8:1083–1101CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Farndale RW (2006) Collagen-induced platelet activation. Blood Cells Mol Dis 36:162–165CrossRefPubMedGoogle Scholar
  72. 72.
    Thunyakitpisal P, Alvarez M, Tokunaga K, Onyia JE, Hock J, Ohashi N, Feister H, Rhodes SJ, Bidwell JP (2001) Cloning and functional analysis of a family of nuclear matrix transcription factors (NP/NMP4) that regulate type I collagen expression in osteoblasts. J Bone Miner Res 16:10–23CrossRefPubMedGoogle Scholar
  73. 73.
    Childress P, Stayrook KR, Alvarez MB, Wang Z, Shao Y, Hernandez-Buquer S, Mack JK, Grese ZR, He Y, Horan D, Pavalko FM, Warden SJ, Robling AG, Yang F-, Allen MR, Krishnan V, Liu Y, Bidwell JP (2015) Genome-wide mapping and interrogation of the Nmp4 antianabolic bone axis. Mol Endocrinol 29:1269–1285CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Hirabayashi S, Ohki K, Nakabayashi K, Ichikawa H, Momozawa Y, Okamura K, Yaguchi A, Terada K, Saito Y, Yoshimi A, Ogata-Kawata H, Sakamoto H, Kato M, Fujimura J, Hino M, Kinoshita A, Kakuda H, Kurosawa H, Kato K, Kajiwara R, Moriwaki K, Morimoto T, Nakamura K, Noguchi Y, Osumi T, Sakashita K, Takita J, Yuza Y, Matsuda K, Yoshida T, Matsumoto K, Hata K, Kubo M, Matsubara Y, Fukushima T, Koh K, Manabe A, Ohara A, Kiyokawa N (2017) ZNF384-related fusion genes define a subgroup of childhood B-cell precursor acute lymphoblastic leukemia with a characteristic immunotype. Haematologica 102:118–129CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Sun Y-, Lu C, Wu Z- (2016) Spinocerebellar ataxia: relationship between phenotype and genotype—a review. Clin Genet 90:305–314CrossRefPubMedGoogle Scholar
  76. 76.
    Liu C, Kelnar K, Liu B, Chen X, Calhoun-Davis T, Li H, Patrawala L, Yan H, Jeter C, Honorio S, Wiggins JF, Bader AG, Fagin R, Brown D, Tang DG (2011) The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44. Nat Med 17:211–216CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Du X, Wang X, Geng M (2018) Alzheimer’s disease hypothesis and related therapies. Transl Neurodegener 7:2CrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Jack CR, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, Holtzman DM, Jagust W, Jessen F, Karlawish J, Liu E, Molinuevo JL, Montine T, Phelps C, Rankin KP, Rowe CC, Scheltens P, Siemers E, Snyder HM, Sperling R, Elliott C, Masliah E, Ryan L, Silverberg N (2018) NIA-AA research framework: toward a biological definition of alzheimer’s disease. Alzheimer’s Dement 14:535–562CrossRefGoogle Scholar
  79. 79.
    Rajgor D (2018) Macro roles for microRNAs in neurodegenerative diseases. Non-coding RNA Res 3:154–159CrossRefGoogle Scholar
  80. 80.
    Bu XL, Xiang Y, Jin WS, Wang J, Shen LL, Huang ZL, Zhang K, Liu YH, Zeng F, Liu JH, Sun HL, Zhuang ZQ, Chen SH, Yao XQ, Giunta B, Shan YC, Tan J, Chen XW, Dong ZF, Zhou HD, Zhou XF, Song W, Wang YJ (2017) Blood-derived amyloid-β protein induces Alzheimer’s disease pathologies. Mol Psychiatry 2017:204Google Scholar
  81. 81.
    Flagmeier P, De S, Wirthensohn DC, Lee SF, Vincke C, Muyldermans S, Knowles TPJ, Gandhi S, Dobson CM, Klenerman D (2017) Ultrasensitive measurement of Ca2+ influx into lipid vesicles induced by protein aggregates. Angew Chem Int Ed 56:7750–7754CrossRefGoogle Scholar
  82. 82.
    Nasica-Labouze J, Nguyen PH, Sterpone F, Berthoumieu O, Buchete N-, Coté S, De Simone A, Doig AJ, Faller P, Garcia A, Laio A, Li MS, Melchionna S, Mousseau N, Mu Y, Paravastu A, Pasquali S, Rosenman DJ, Strodel B, Tarus B, Viles JH, Zhang T, Wang C, Derreumaux P (2015) Amyloid β protein and alzheimer’s disease: when computer simulations complement experimental studies. Chem Rev 115:3518–3563CrossRefPubMedPubMedCentralGoogle Scholar
  83. 83.
    Vivekanandan S, Brender JR, Lee SY, Ramamoorthy A (2011) A partially folded structure of amyloid-beta(1-40) in an aqueous environment. Biochem Biophys Res Commun 411:312–316CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Sgourakis NG, Yan Y, McCallum SA, Wang C, Garcia AE (2007) The alzheimer’s peptides Aβ40 and 42 adopt distinct conformations in water: a combined MD/NMR study. J Mol Biol 368:1448–1457CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    Schonrock N, Ke YD, Humphreys D, Staufenbiel M, Ittner LM, Preiss T, Götz J (2010) Neuronal micro RNA deregulation in response to alzheimer’s disease amyloid-β. PLoS One 5:e11070CrossRefPubMedPubMedCentralGoogle Scholar
  86. 86.
    Chang F, Zhang L-, Xu WU-, Jing P, Zhan P- (2014) microRNA-9 attenuates amyloidβ-induced synaptotoxicity by targeting calcium/calmodulin-dependent protein kinase kinase 2. Mol Med Rep 9:1917–1922CrossRefPubMedGoogle Scholar
  87. 87.
    Colvin MT, Silvers R, Ni QZ, Can TV, Sergeyev I, Rosay M, Donovan KJ, Michael B, Wall J, Linse S, Griffin RG (2016) Atomic resolution structure of monomorphic Aβ42Amyloid fibrils. J Am Chem Soc 138:9663–9674CrossRefPubMedPubMedCentralGoogle Scholar
  88. 88.
    Jankovic J (2008) Parkinson’s disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatry 79:368–376CrossRefPubMedGoogle Scholar
  89. 89.
    Schulz-Schaeffer WJ (2010) The synaptic pathology of α-synuclein aggregation in dementia with lewy bodies, parkinson’s disease and parkinson’s disease dementia. Acta Neuropathol 120:131–143CrossRefPubMedPubMedCentralGoogle Scholar
  90. 90.
    Bartels T, Choi JG, Selkoe DJ (2011) α-Synuclein occurs physiologically as a helically folded tetramer that resists aggregation. Nature 477:107–111CrossRefPubMedPubMedCentralGoogle Scholar
  91. 91.
    Alvarez-Erviti L, Seow Y, Schapira AHV, Rodriguez-Oroz MC, Obeso JA, Cooper JM (2013) Influence of microRNA deregulation on chaperone-mediated autophagy and α-synuclein pathology in parkinson’s disease. Cell Death Dis 4:e545CrossRefPubMedPubMedCentralGoogle Scholar
  92. 92.
    Doxakis E (2010) Post-transcriptional regulation of α-synuclein expression by mir-7 and mir-153. J Biol Chem 285:12726–12734CrossRefPubMedPubMedCentralGoogle Scholar
  93. 93.
    Choi DC, Yoo M, Kabaria S, Junn E (2018) MicroRNA-7 facilitates the degradation of alpha-synuclein and its aggregates by promoting autophagy. Neurosci Lett 678:118–123CrossRefPubMedGoogle Scholar
  94. 94.
    Ma W, Li Y, Wang C, Xu F, Wang M, Liu Y (2016) Serum miR-221 serves as a biomarker for parkinson’s disease. Cell Biochem Funct 34:511–515CrossRefPubMedGoogle Scholar
  95. 95.
    Li L, Xu J, Wu M, Hu JM (2018) Protective role of microRNA-221 in parkinson’s disease. Bratislava Med J 119:22–27CrossRefGoogle Scholar
  96. 96.
    Geschwind MD (2015) Prion diseases. Continuum. Lifelong Learn Neurol 21:1612–1638CrossRefGoogle Scholar
  97. 97.
    Asante EA, Smidak M, Grimshaw A, Houghton R, Tomlinson A, Jeelani A, Jakubcova T, Hamdan S, Richard-Londt A, Linehan JM, Brandner S, Alpers M, Whitfield J, Mead S, Wadsworth JDF, Collinge J (2015) A naturally occurring variant of the human prion protein completely prevents prion disease. Nature 522:478–481CrossRefPubMedPubMedCentralGoogle Scholar
  98. 98.
    Lloyd SE, Mead S, Collinge J (2013) Genetics of prion diseases. Curr Opin Genet Dev 23:345–351CrossRefPubMedPubMedCentralGoogle Scholar
  99. 99.
    Biljan I, Giachin G, Ilc G, Zhukov I, Plavec J, Legname G (2012) Structural basis for the protective effect of the human prion protein carrying the dominant-negative E219K polymorphism. Biochem J 446:243–251CrossRefPubMedGoogle Scholar
  100. 100.
    Boese AS, Saba R, Campbell K, Majer A, Medina S, Burton L, Booth TF, Chong P, Westmacott G, Dutta SM, Saba JA, Booth SA (2016) MicroRNA abundance is altered in synaptoneurosomes during prion disease. Mol Cell Neurosci 71:13–24CrossRefPubMedGoogle Scholar
  101. 101.
    Montag J, Hitt R, Opitz L, Schulz-Schaeffer WJ, Hunsmann G, Motzkus D (2009) Upregulation of miRNA hsa-miR-342-3p in experimental and idiopathic prion disease. Mol Neurodegener 4:36CrossRefPubMedPubMedCentralGoogle Scholar
  102. 102.
    Bellingham SA, Coleman BM, Hill AF (2012) Small RNA deep sequencing reveals a distinct miRNA signature released in exosomes from prion-infected neuronal cells. Nucleic Acids Res 40:10937–10949CrossRefPubMedPubMedCentralGoogle Scholar
  103. 103.
    Nahalka J, Hrabarova E, Talafova K (2015) Protein-RNA and protein-glycan recognitions in light of amino acid codes. Biochim Biophys Acta Gen Subj 1850:1942–1952CrossRefGoogle Scholar

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Institute of Chemistry, Centre for Glycomics, Slovak Academy of SciencesBratislavaSlovak Republic
  2. 2.Institute of Chemistry, Centre of Excellence for White-green Biotechnology, Slovak Academy of SciencesNitraSlovak Republic

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