Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Molecular landscape of long noncoding RNAs in brain disorders

Molecular Psychiatry volume 26, pages 1060–1074 (2021)Cite this article

Subjects

Abstract

According to current paradigms, various risk factors, such as genetic mutations, oxidative stress, neural network dysfunction, and abnormal protein degradation, contribute to the progression of brain disorders. Through the cooperation of gene transcripts in biological processes, the study of noncoding RNAs can lead to insights into the cause and treatment of brain disorders. Recently, long noncoding RNAs (lncRNAs) which are longer than 200 nucleotides in length have been suggested as key factors in various brain disorders. Accumulating evidence suggests the potential of lncRNAs as diagnostic or prognostic biomarkers and therapeutic targets. High-throughput screening-based sequencing has been instrumental in identification of lncRNAs that demand new approaches to understanding the progression of brain disorders. In this review, we discuss the recent progress in the study of lncRNAs, and addresses the pathogenesis of brain disorders that involve lncRNAs and describes the associations of lncRNAs with neurodegenerative disorders such as Alzheimer disease (AD), Parkinson disease (PD), and neurodevelopmental disorders. We also discuss potential targets of lncRNAs and their promise as novel therapeutics and biomarkers in brain disorders.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Functional classifications and pathological functions of lncRNAs.
Fig. 2: Annotations of lncRNAs.

Similar content being viewed by others

References

  1. Doolittle WF. Is junk DNA bunk? A critique of ENCODE. Proc Natl Acad Sci USA. 2013;110:5294–300.

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Djebali S, Davis CA, Merkel A, Dobin A, Lassmann T, Mortazavi A, et al. Landscape of transcription in human cells. Nature. 2012;489:101–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Kopp F, Mendell JT. Functional classification and experimental dissection of long noncoding RNAs. Cell. 2018;172:393–407.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Slack FJ, Chinnaiyan AM. The role of non-coding RNAs in oncology. Cell. 2019;179:1033–55.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Sana J, Faltejskova P, Svoboda M, Slaby O. Novel classes of non-coding RNAs and cancer. J Transl Med. 2012;10:103.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Rinn JL, Chang HY. Genome regulation by long noncoding RNAs. Annu Rev Biochem. 2012;81:145–66.

    CAS  PubMed  Google Scholar 

  7. Brown CJ, Ballabio A, Rupert JL, Lafreniere RG, Grompe M, Tonlorenzi R, et al. A gene from the region of the human X inactivation centre is expressed exclusively from the inactive X chromosome. Nature. 1991;349:38–44.

    CAS  PubMed  Google Scholar 

  8. Bartolomei MS, Zemel S, Tilghman SM. Parental imprinting of the mouse H19 gene. Nature. 1991;351:153–5.

    CAS  PubMed  Google Scholar 

  9. Nojima T, Tellier M, Foxwell J, Ribeiro de Almeida C, Tan-Wong SM, Dhir S, et al. Deregulated expression of mammalian lncRNA through loss of SPT6 induces R-loop formation, replication stress, and cellular senescence. Mol Cell. 2018;72:970–84.e77.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Sati S, Ghosh S, Jain V, Scaria V, Sengupta S. Genome-wide analysis reveals distinct patterns of epigenetic features in long non-coding RNA loci. Nucleic Acids Res. 2012;40:10018–31.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Zhao Y, Li H, Fang S, Kang Y, Wu W, Hao Y, et al. NONCODE 2016: an informative and valuable data source of long non-coding RNAs. Nucleic Acids Res. 2016;44:D203–8.

    CAS  PubMed  Google Scholar 

  12. Uszczynska-Ratajczak B, Lagarde J, Frankish A, Guigo R, Johnson R. Towards a complete map of the human long non-coding RNA transcriptome. Nat Rev Genet. 2018;19:535–48.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Kim TK, Hemberg M, Gray JM. Enhancer RNAs: a class of long noncoding RNAs synthesized at enhancers. Cold Spring Harb Perspect Biol. 2015;7:a018622.

    PubMed  PubMed Central  Google Scholar 

  14. Joo JY, Schaukowitch K, Farbiak L, Kilaru G, Kim TK. Stimulus-specific combinatorial functionality of neuronal c-fos enhancers. Nat Neurosci. 2016;19:75–83.

    CAS  PubMed  Google Scholar 

  15. Schaukowitch K, Joo JY, Liu X, Watts JK, Martinez C, Kim TK. Enhancer RNA facilitates NELF release from immediate early genes. Mol Cell. 2014;56:29–42.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Kim TK, Shiekhattar R. Architectural and functional commonalities between enhancers and promoters. Cell. 2015;162:948–59.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Rinn JL, Chang HY. Long noncoding RNAs: molecular modalities to organismal functions. Annu Rev Biochem. 2020;89:283–308.

    CAS  PubMed  Google Scholar 

  18. Salta E, De Strooper B. Noncoding RNAs in neurodegeneration. Nat Rev Neurosci. 2017;18:627–40.

    CAS  PubMed  Google Scholar 

  19. Clemson CM, Hutchinson JN, Sara SA, Ensminger AW, Fox AH, Chess A, et al. An architectural role for a nuclear noncoding RNA: NEAT1 RNA is essential for the structure of paraspeckles. Mol Cell. 2009;33:717–26.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Kerin T, Ramanathan A, Rivas K, Grepo N, Coetzee GA, Campbell DB. A noncoding RNA antisense to moesin at 5p14.1 in autism. Sci Transl Med. 2012;4:128ra140.

    Google Scholar 

  21. Velmeshev D, Magistri M, Faghihi MA. Expression of non-protein-coding antisense RNAs in genomic regions related to autism spectrum disorders. Mol Autism. 2013;4:32.

    PubMed  PubMed Central  Google Scholar 

  22. Liu Y, Chen YY, Liu H, Yao CJ, Zhu XX, Chen DJ, et al. Association between ubiquitin carboxy-terminal hydrolase-L1 S18Y variant and risk of Parkinson’s disease: the impact of ethnicity and onset age. Neurol Sci. 2015;36:179–88.

    CAS  PubMed  Google Scholar 

  23. Carrieri C, Forrest AR, Santoro C, Persichetti F, Carninci P, Zucchelli S, et al. 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 Cell Neurosci. 2015;9:114.

    PubMed  PubMed Central  Google Scholar 

  24. Tromp D, Dufour A, Lithfous S, Pebayle T, Despres O. Episodic memory in normal aging and Alzheimer disease: Insights from imaging and behavioral studies. Ageing Res Rev. 2015;24:232–62.

    CAS  PubMed  Google Scholar 

  25. Galvao F Jr, Grokoski KC, da Silva BB, Lamers ML, Siqueira IR. The amyloid precursor protein (APP) processing as a biological link between Alzheimer’s disease and cancer. Ageing Res Rev. 2019;49:83–91.

    CAS  PubMed  Google Scholar 

  26. Faghihi MA, Modarresi F, Khalil AM, Wood DE, Sahagan BG, Morgan TE, et al. Expression of a noncoding RNA is elevated in Alzheimer’s disease and drives rapid feed-forward regulation of beta-secretase. Nat Med. 2008;14:723–30.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Faghihi MA, Zhang M, Huang J, Modarresi F, Van der Brug MP, Nalls MA, et al. Evidence for natural antisense transcript-mediated inhibition of microRNA function. Genome Biol. 2010;11:R56.

    PubMed  PubMed Central  Google Scholar 

  28. Zeng T, Ni H, Yu Y, Zhang M, Wu M, Wang Q, et al. BACE1-AS prevents BACE1 mRNA degradation through the sequestration of BACE1-targeting miRNAs. J Chem Neuroanat. 2019;98:87–96.

    CAS  PubMed  Google Scholar 

  29. Das B, Yan R. Role of BACE1 in Alzheimer’s synaptic function. Transl Neurodegener. 2017;6:23.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Wang P, Zheng X, Guo Q, Yang P, Pang X, Qian K, et al. Systemic delivery of BACE1 siRNA through neuron-targeted nanocomplexes for treatment of Alzheimer’s disease. J Control Release. 2018;279:220–33.

    CAS  PubMed  Google Scholar 

  31. Sosinska P, Mikula-Pietrasik J, Ksiazek K. The double-edged sword of long non-coding RNA: the role of human brain-specific BC200 RNA in translational control, neurodegenerative diseases, and cancer. Mutat Res Rev Mutat Res. 2015;766:58–67.

    CAS  PubMed  Google Scholar 

  32. Chen W, Bocker W, Brosius J, Tiedge H. Expression of neural BC200 RNA in human tumours. J Pathol. 1997;183:345–51.

    CAS  PubMed  Google Scholar 

  33. Singh R, Gupta SC, Peng WX, Zhou N, Pochampally R, Atfi A, et al. Regulation of alternative splicing of Bcl-x by BC200 contributes to breast cancer pathogenesis. Cell Death Dis. 2016;7:e2262.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Booy EP, McRae EK, Koul A, Lin F, McKenna SA. The long non-coding RNA BC200 (BCYRN1) is critical for cancer cell survival and proliferation. Mol Cancer. 2017;16:109.

    PubMed  PubMed Central  Google Scholar 

  35. Mus E, Hof PR, Tiedge H. Dendritic BC200 RNA in aging and in Alzheimer’s disease. Proc Natl Acad Sci USA. 2007;104:10679–84.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Li H, Zheng L, Jiang A, Mo Y, Gong Q. Identification of the biological affection of long noncoding RNA BC200 in Alzheimer’s disease. Neuroreport. 2018;29:1061–7.

    CAS  PubMed  Google Scholar 

  37. Lukiw WJ, Handley P, Wong L, Crapper McLachlan DR. BC200 RNA in normal human neocortex, non-Alzheimer dementia (NAD), and senile dementia of the Alzheimer type (AD). Neurochem Res. 1992;17:591–7.

    CAS  PubMed  Google Scholar 

  38. Fatemi SH, Folsom TD, Reutiman TJ, Thuras PD. Expression of GABA(B) receptors is altered in brains of subjects with autism. Cerebellum. 2009;8:64–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Massone S, Vassallo I, Fiorino G, Castelnuovo M, Barbieri F, Borghi R, et al. 17A, a novel non-coding RNA, regulates GABA B alternative splicing and signaling in response to inflammatory stimuli and in Alzheimer disease. Neurobiol Dis. 2011;41:308–17.

    CAS  PubMed  Google Scholar 

  40. Ciarlo E, Massone S, Penna I, Nizzari M, Gigoni A, Dieci G, et al. An intronic ncRNA-dependent regulation of SORL1 expression affecting Abeta formation is upregulated in post-mortem Alzheimer’s disease brain samples. Dis Model Mech. 2013;6:424–33.

    CAS  PubMed  Google Scholar 

  41. K TC, Lunetta KL, Baldwin CT, McKee AC, Guo J, Cupples LA, et al. Association of distinct variants in SORL1 with cerebrovascular and neurodegenerative changes related to Alzheimer disease. Arch Neurol. 2008;65:1640–8.

    Google Scholar 

  42. Rogaeva E, Meng Y, Lee JH, Gu Y, Kawarai T, Zou F, et al. The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease. Nat Genet. 2007;39:168–77.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Deng YY, Xiao L, Li W, Tian M, Feng XL, Feng H, et al. Plasma long noncoding RNA 51A as a stable biomarker of Alzheimer’s disease. Int J Clin Exp Pathol. 2017;10:4694–9.

    CAS  Google Scholar 

  44. Song M, Martinowich K, Lee FS. BDNF at the synapse: why location matters. Mol Psychiatry. 2017;22:1370–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Zuccato C, Cattaneo E. Brain-derived neurotrophic factor in neurodegenerative diseases. Nat Rev Neurol. 2009;5:311–22.

    CAS  PubMed  Google Scholar 

  46. Modarresi F, Faghihi MA, Lopez-Toledano MA, Fatemi RP, Magistri M, Brothers SP, et al. Inhibition of natural antisense transcripts in vivo results in gene-specific transcriptional upregulation. Nat Biotechnol. 2012;30:453–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Guo CC, Jiao CH, Gao ZM. Silencing of LncRNA BDNF-AS attenuates Abeta25-35-induced neurotoxicity in PC12 cells by suppressing cell apoptosis and oxidative stress. Neurol Res. 2018;40:795–804.

    CAS  PubMed  Google Scholar 

  48. Huang J, Huen MS, Kim H, Leung CC, Glover JN, Yu X, et al. RAD18 transmits DNA damage signalling to elicit homologous recombination repair. Nat Cell Biol. 2009;11:592–603.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Parenti R, Paratore S, Torrisi A, Cavallaro S. A natural antisense transcript against Rad18, specifically expressed in neurons and upregulated during beta-amyloid-induced apoptosis. Eur J Neurosci. 2007;26:2444–57.

    PubMed  Google Scholar 

  50. Castelnuovo M, Massone S, Tasso R, Fiorino G, Gatti M, Robello M, et al. An Alu-like RNA promotes cell differentiation and reduces malignancy of human neuroblastoma cells. FASEB J. 2010;24:4033–46.

    CAS  PubMed  Google Scholar 

  51. Massone S, Ciarlo E, Vella S, Nizzari M, Florio T, Russo C, et al. NDM29, a RNA polymerase III-dependent non coding RNA, promotes amyloidogenic processing of APP and amyloid beta secretion. Biochim Biophys Acta. 2012;1823:1170–7.

    CAS  PubMed  Google Scholar 

  52. Kinney JW, Bemiller SM, Murtishaw AS, Leisgang AM, Salazar AM, Lamb BT. Inflammation as a central mechanism in Alzheimer’s disease. Alzheimers Dement. 2018;4:575–90.

    Google Scholar 

  53. Clarkson ED, Zawada WM, Freed CR. GDNF improves survival and reduces apoptosis in human embryonic dopaminergic neurons in vitro. Cell Tissue Res. 1997;289:207–10.

    CAS  PubMed  Google Scholar 

  54. Ayanlaja AA, Zhang B, Ji G, Gao Y, Wang J, Kanwore K, et al. The reversible effects of glial cell line-derived neurotrophic factor (GDNF) in the human brain. Semin Cancer Biol. 2018;53:212–22.

    CAS  PubMed  Google Scholar 

  55. Sherer TB, Fiske BK, Svendsen CN, Lang AE, Langston JW. Crossroads in GDNF therapy for Parkinson’s disease. Mov Disord. 2006;21:136–41.

    PubMed  Google Scholar 

  56. Gill SS, Patel NK, Hotton GR, O’Sullivan K, McCarter R, Bunnage M, et al. Direct brain infusion of glial cell line-derived neurotrophic factor in Parkinson disease. Nat Med. 2003;9:589–95.

    CAS  PubMed  Google Scholar 

  57. Straten G, Eschweiler GW, Maetzler W, Laske C, Leyhe T. Glial cell-line derived neurotrophic factor (GDNF) concentrations in cerebrospinal fluid and serum of patients with early Alzheimer’s disease and normal controls. J Alzheimers Dis. 2009;18:331–7.

    CAS  PubMed  Google Scholar 

  58. Airavaara M, Pletnikova O, Doyle ME, Zhang YE, Troncoso JC, Liu QR. Identification of novel GDNF isoforms and cis-antisense GDNFOS gene and their regulation in human middle temporal gyrus of Alzheimer disease. J Biol Chem. 2011;286:45093–102.

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Poewe W, Seppi K, Tanner CM, Halliday GM, Brundin P, Volkmann J, et al. Parkinson disease. Nat Rev Dis Prim. 2017;3:17013.

    PubMed  Google Scholar 

  60. DeMaagd G, Philip A. Parkinson’s disease and its management: part 1: disease entity, risk factors, pathophysiology, clinical presentation, and diagnosis. P T. 2015;40:504–32.

    PubMed  PubMed Central  Google Scholar 

  61. Chaudhuri KR, Healy DG, Schapira AH. National Institute for Clinical E. Non-motor symptoms of Parkinson’s disease: diagnosis and management. Lancet Neurol. 2006;5:235–45.

    PubMed  Google Scholar 

  62. Stefanis L. alpha-Synuclein in Parkinson’s disease. Cold Spring Harb Perspect Med. 2012;2:a009399.

    PubMed  PubMed Central  Google Scholar 

  63. Elkouris M, Kouroupi G, Vourvoukelis A, Papagiannakis N, Kaltezioti V, Matsas R, et al. Long non-coding RNAs associated with neurodegeneration-linked genes are reduced in parkinson’s disease patients. Front Cell Neurosci. 2019;13:58.

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Lim KH, Joo JY, Baek KH. The potential roles of deubiquitinating enzymes in brain diseases. Ageing Res Rev. 2020;61:101088.

    CAS  PubMed  Google Scholar 

  65. Bilguvar K, Tyagi NK, Ozkara C, Tuysuz B, Bakircioglu M, Choi M, et al. Recessive loss of function of the neuronal ubiquitin hydrolase UCHL1 leads to early-onset progressive neurodegeneration. Proc Natl Acad Sci USA. 2013;110:3489–94.

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Liu H, Povysheva N, Rose ME, Mi Z, Banton JS, Li W, et al. Role of UCHL1 in axonal injury and functional recovery after cerebral ischemia. Proc Natl Acad Sci USA. 2019;116:4643–50.

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Healy DG, Abou-Sleiman PM, Casas JP, Ahmadi KR, Lynch T, Gandhi S, et al. UCHL-1 is not a Parkinson’s disease susceptibility gene. Ann Neurol. 2006;59:627–33.

    CAS  PubMed  Google Scholar 

  68. Liu Y, Fallon L, Lashuel HA, Liu Z, Lansbury PT Jr. The UCH-L1 gene encodes two opposing enzymatic activities that affect alpha-synuclein degradation and Parkinson’s disease susceptibility. Cell. 2002;111:209–18.

    CAS  PubMed  Google Scholar 

  69. Maraganore DM, Lesnick TG, Elbaz A, Chartier-Harlin MC, Gasser T, Kruger R, et al. UCHL1 is a Parkinson’s disease susceptibility gene. Ann Neurol. 2004;55:512–21.

    PubMed  Google Scholar 

  70. Riva P, Ratti A, Venturin M. The Long Non-Coding RNAs in Neurodegenerative Diseases: Novel Mechanisms of Pathogenesis. Curr Alzheimer Res. 2016;13:1219–31.

    CAS  PubMed  Google Scholar 

  71. Carrieri C, Cimatti L, Biagioli M, Beugnet A, Zucchelli S, Fedele S, et al. Long non-coding antisense RNA controls Uchl1 translation through an embedded SINEB2 repeat. Nature. 2012;491:454–7.

    CAS  PubMed  Google Scholar 

  72. Deas E, Plun-Favreau H, Wood NW. PINK1 function in health and disease. EMBO Mol Med. 2009;1:152–65.

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Pickrell AM, Youle RJ. The roles of PINK1, parkin, and mitochondrial fidelity in Parkinson’s disease. Neuron. 2015;85:257–73.

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Valente EM, Abou-Sleiman PM, Caputo V, Muqit MM, Harvey K, Gispert S, et al. Hereditary early-onset Parkinson’s disease caused by mutations in PINK1. Science. 2004;304:1158–60.

    CAS  PubMed  Google Scholar 

  75. Simchovitz A, Hanan M, Niederhoffer N, Madrer N, Yayon N, Bennett ER, et al. NEAT1 is overexpressed in Parkinson’s disease substantia nigra and confers drug-inducible neuroprotection from oxidative stress. FASEB J. 2019;33:11223–34.

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Scheele C, Petrovic N, Faghihi MA, Lassmann T, Fredriksson K, Rooyackers O, et al. The human PINK1 locus is regulated in vivo by a non-coding natural antisense RNA during modulation of mitochondrial function. BMC Genom. 2007;8:74.

    Google Scholar 

  77. Boros FA, Maszlag-Torok R, Vecsei L, Klivenyi P. Increased level of NEAT1 long non-coding RNA is detectable in peripheral blood cells of patients with Parkinson’s disease. Brain Res. 2020;1730:146672.

    CAS  PubMed  Google Scholar 

  78. Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 2010;464:1071–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Lang Y, Li Y, Yu H, Lin L, Chen X, Wang S, et al. HOTAIR drives autophagy in midbrain dopaminergic neurons in the substantia nigra compacta in a mouse model of Parkinson’s disease by elevating NPTX2 via miR-221-3p binding. Aging. 2020;12:7660–78.

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Lin Q, Hou S, Dai Y, Jiang N, Lin Y. LncRNA HOTAIR targets miR-126-5p to promote the progression of Parkinson’s disease through RAB3IP. Biol Chem. 2019;400:1217–28.

    CAS  PubMed  Google Scholar 

  81. Shirvani Farsani Z, Zahirodin A, Ghaderian SMH, Shams J, Naghavi Gargari B. The role of long non-coding RNA MALAT1 in patients with bipolar disorder. Metab Brain Dis. 2020;35:1077–83.

    CAS  PubMed  Google Scholar 

  82. Kouroupi G, Taoufik E, Vlachos IS, Tsioras K, Antoniou N, Papastefanaki F, et al. Defective synaptic connectivity and axonal neuropathology in a human iPSC-based model of familial Parkinson’s disease. Proc Natl Acad Sci USA. 2017;114:E3679–88.

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Zhang X, Hamblin MH, Yin KJ. The long noncoding RNA Malat1: its physiological and pathophysiological functions. RNA Biol. 2017;14:1705–14.

    PubMed  PubMed Central  Google Scholar 

  84. Kraus TFJ, Haider M, Spanner J, Steinmaurer M, Dietinger V, Kretzschmar HA. Altered long noncoding RNA expression precedes the course of Parkinson’s disease-a preliminary report. Mol Neurobiol. 2017;54:2869–77.

    CAS  PubMed  Google Scholar 

  85. Liu W, Zhang Q, Zhang J, Pan W, Zhao J, Xu Y. Long non-coding RNA MALAT1 contributes to cell apoptosis by sponging miR-124 in Parkinson disease. Cell Biosci. 2017;7:19.

    PubMed  PubMed Central  Google Scholar 

  86. Satoh J, Tabunoki H, Arima K. Molecular network analysis suggests aberrant CREB-mediated gene regulation in the Alzheimer disease hippocampus. Dis Markers. 2009;27:239–52.

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Yao J, Wang XQ, Li YJ, Shan K, Yang H, Wang YN, et al. Long non-coding RNA MALAT1 regulates retinal neurodegeneration through CREB signaling. EMBO Mol Med. 2016;8:346–62.

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Tobin JE, Latourelle JC, Lew MF, Klein C, Suchowersky O, Shill HA, et al. Haplotypes and gene expression implicate the MAPT region for Parkinson disease: the GenePD Study. Neurology. 2008;71:28–34.

    CAS  PubMed  Google Scholar 

  89. Coupland KG, Kim WS, Halliday GM, Hallupp M, Dobson-Stone C, Kwok JB. Role of the long non-coding RNA MAPT-AS1 in regulation of microtubule associated protein tau (MAPT) expression in Parkinson’s disease. PLoS ONE. 2016;11:e0157924.

    PubMed  PubMed Central  Google Scholar 

  90. Das G, Misra AK, Das SK, Ray K, Ray J. Microtubule-associated protein tau (MAPT) influences the risk of Parkinson’s disease among Indians. Neurosci Lett. 2009;460:16–20.

    CAS  PubMed  Google Scholar 

  91. Ni Y, Huang H, Chen Y, Cao M, Zhou H, Zhang Y. Investigation of long non-coding RNA expression profiles in the substantia nigra of Parkinson’s disease. Cell Mol Neurobiol. 2017;37:329–38.

    CAS  PubMed  Google Scholar 

  92. Ross CA, Poirier MA. Protein aggregation and neurodegenerative disease. Nat Med. 2004;10 Suppl:S10–17.

    PubMed  Google Scholar 

  93. De Souza RA, Leavitt BR. Neurobiology of Huntington’s disease. Curr Top Behav Neurosci. 2015;22:81–100.

    PubMed  Google Scholar 

  94. Bates GP, Dorsey R, Gusella JF, Hayden MR, Kay C, Leavitt BR, et al. Huntington disease. Nat Rev Dis Prim. 2015;1:15005.

    PubMed  Google Scholar 

  95. Wild EJ, Tabrizi SJ. Therapies targeting DNA and RNA in Huntington’s disease. Lancet Neurol. 2017;16:837–47.

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Chung DW, Rudnicki DD, Yu L, Margolis RL. A natural antisense transcript at the Huntington’s disease repeat locus regulates HTT expression. Hum Mol Genet. 2011;20:3467–77.

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Hwang JY, Zukin RS. REST, a master transcriptional regulator in neurodegenerative disease. Curr Opin Neurobiol. 2018;48:193–200.

    CAS  PubMed  PubMed Central  Google Scholar 

  98. Johnson R, Richter N, Jauch R, Gaughwin PM, Zuccato C, Cattaneo E, et al. Human accelerated region 1 noncoding RNA is repressed by REST in Huntington’s disease. Physiol Genom. 2010;41:269–74.

    CAS  Google Scholar 

  99. Zhang Q, Geng PL, Yin P, Wang XL, Jia JP, Yao J. Down-regulation of long non-coding RNA TUG1 inhibits osteosarcoma cell proliferation and promotes apoptosis. Asian Pac J Cancer Prev. 2013;14:2311–5.

    PubMed  Google Scholar 

  100. Xu Y, Wang J, Qiu M, Xu L, Li M, Jiang F, et al. Upregulation of the long noncoding RNA TUG1 promotes proliferation and migration of esophageal squamous cell carcinoma. Tumour Biol. 2015;36:1643–51.

    CAS  PubMed  Google Scholar 

  101. Li Q, Zhang J, Su DM, Guan LN, Mu WH, Yu M, et al. lncRNA TUG1 modulates proliferation, apoptosis, invasion, and angiogenesis via targeting miR-29b in trophoblast cells. Hum Genom. 2019;13:50.

    Google Scholar 

  102. Chen C, Cheng G, Yang X, Li C, Shi R, Zhao N. Tanshinol suppresses endothelial cells apoptosis in mice with atherosclerosis via lncRNA TUG1 up-regulating the expression of miR-26a. Am J Transl Res. 2016;8:2981–91.

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Johnson R. Long non-coding RNAs in Huntington’s disease neurodegeneration. Neurobiol Dis. 2012;46:245–54.

    CAS  PubMed  Google Scholar 

  104. Khalil AM, Guttman M, Huarte M, Garber M, Raj A, Rivea Morales D, et al. Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc Natl Acad Sci USA. 2009;106:11667–72.

    CAS  PubMed  PubMed Central  Google Scholar 

  105. Sunwoo JS, Lee ST, Im W, Lee M, Byun JI, Jung KH, et al. Altered expression of the long noncoding RNA NEAT1 in Huntington’s disease. Mol Neurobiol. 2017;54:1577–86.

    CAS  PubMed  Google Scholar 

  106. Cheng C, Spengler RM, Keiser MS, Monteys AM, Rieders JM, Ramachandran S, et al. The long non-coding RNA NEAT1 is elevated in polyglutamine repeat expansion diseases and protects from disease gene-dependent toxicities. Hum Mol Genet. 2018;27:4303–14.

    CAS  PubMed  PubMed Central  Google Scholar 

  107. Zhang X, Rice K, Wang Y, Chen W, Zhong Y, Nakayama Y, et al. Maternally expressed gene 3 (MEG3) noncoding ribonucleic acid: isoform structure, expression, and functions. Endocrinology. 2010;151:939–47.

    CAS  PubMed  Google Scholar 

  108. Al-Rugeebah A, Alanazi M, Parine NR. MEG3: an oncogenic long non-coding RNA in different cancers. Pathol Oncol Res. 2019;25:859–74.

    CAS  PubMed  Google Scholar 

  109. Chanda K, Das S, Chakraborty J, Bucha S, Maitra A, Chatterjee R, et al. Altered levels of long NcRNAs Meg3 and Neat1 in cell and animal models of Huntington’s disease. RNA Biol. 2018;15:1348–63.

    PubMed  PubMed Central  Google Scholar 

  110. Brochier C, Gaillard MC, Diguet E, Caudy N, Dossat C, Segurens B, et al. Quantitative gene expression profiling of mouse brain regions reveals differential transcripts conserved in human and affected in disease models. Physiol Genom. 2008;33:170–9.

    CAS  Google Scholar 

  111. Lord CC, Thomas G, Brown JM. Mammalian alpha beta hydrolase domain (ABHD) proteins: Lipid metabolizing enzymes at the interface of cell signaling and energy metabolism. Biochim Biophys Acta. 2013;1831:792–802.

    CAS  PubMed  PubMed Central  Google Scholar 

  112. Zhuang X, Tong H, Ding Y, Wu L, Cai J, Si Y, et al. Long noncoding RNA ABHD11-AS1 functions as a competing endogenous RNA to regulate papillary thyroid cancer progression by miR-199a-5p/SLC1A5 axis. Cell Death Dis. 2019;10:620.

    PubMed  PubMed Central  Google Scholar 

  113. Park H, Miyazaki H, Yamanaka T, Nukina N. Non-coding RNA Neat1 and Abhd11os expressions are dysregulated in medium spiny neurons of Huntington disease model mice. Neurosci Res. 2019;147:58–63.

    CAS  PubMed  Google Scholar 

  114. Farrer LA, Cupples LA, Haines JL, Hyman B, Kukull WA, Mayeux R, et al. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer disease meta analysis consortium. JAMA. 1997;278:1349–56.

    CAS  PubMed  Google Scholar 

  115. Rojas C, Barnaeva E, Thomas AG, Hu X, Southall N, Marugan J, et al. DPTIP, a newly identified potent brain penetrant neutral sphingomyelinase 2 inhibitor, regulates astrocyte-peripheral immune communication following brain inflammation. Sci Rep. 2018;8:17715.

    CAS  PubMed  PubMed Central  Google Scholar 

  116. Adams JS, Adams PE, Nguyen D, Brunberg JA, Tassone F, Zhang W, et al. Volumetric brain changes in females with fragile X-associated tremor/ataxia syndrome (FXTAS). Neurology. 2007;69:851–9.

    CAS  PubMed  Google Scholar 

  117. Hagerman P. Fragile X-associated tremor/ataxia syndrome (FXTAS): pathology and mechanisms. Acta Neuropathol. 2013;126:1–19.

    CAS  PubMed  PubMed Central  Google Scholar 

  118. Ladd PD, Smith LE, Rabaia NA, Moore JM, Georges SA, Hansen RS, et al. An antisense transcript spanning the CGG repeat region of FMR1 is upregulated in premutation carriers but silenced in full mutation individuals. Hum Mol Genet. 2007;16:3174–87.

    CAS  PubMed  Google Scholar 

  119. Pastori C, Peschansky VJ, Barbouth D, Mehta A, Silva JP, Wahlestedt C. Comprehensive analysis of the transcriptional landscape of the human FMR1 gene reveals two new long noncoding RNAs differentially expressed in Fragile X syndrome and Fragile X-associated tremor/ataxia syndrome. Hum Genet. 2014;133:59–67.

    CAS  PubMed  Google Scholar 

  120. Monani UR. Spinal muscular atrophy: a deficiency in a ubiquitous protein; a motor neuron-specific disease. Neuron. 2005;48:885–96.

    CAS  PubMed  Google Scholar 

  121. Hamilton G, Gillingwater TH. Spinal muscular atrophy: going beyond the motor neuron. Trends Mol Med. 2013;19:40–50.

    CAS  PubMed  Google Scholar 

  122. d’Ydewalle C, Ramos DM, Pyles NJ, Ng SY, Gorz M, Pilato CM, et al. The antisense transcript SMN-AS1 regulates SMN expression and is a novel therapeutic target for spinal muscular atrophy. Neuron. 2017;93:66–79.

    PubMed  Google Scholar 

  123. Corral-Juan M, Serrano-Munuera C, Rabano A, Cota-Gonzalez D, Segarra-Roca A, Ispierto L, et al. Clinical, genetic and neuropathological characterization of spinocerebellar ataxia type 37. Brain. 2018;141:1981–97.

    PubMed  Google Scholar 

  124. Klockgether T, Mariotti C, Paulson HL. Spinocerebellar ataxia. Nat Rev Dis Prim. 2019;5:24.

    PubMed  Google Scholar 

  125. Scoles DR, Meera P, Schneider MD, Paul S, Dansithong W, Figueroa KP, et al. Antisense oligonucleotide therapy for spinocerebellar ataxia type 2. Nature. 2017;544:362–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  126. Tan JY, Vance KW, Varela MA, Sirey T, Watson LM, Curtis HJ, et al. Cross-talking noncoding RNAs contribute to cell-specific neurodegeneration in SCA7. Nat Struct Mol Biol. 2014;21:955–61.

    CAS  PubMed  PubMed Central  Google Scholar 

  127. Evert BO, Nalavade R, Jungverdorben J, Matthes F, Weber S, Rajput A, et al. Upregulation of miR-370 and miR-543 is associated with reduced expression of heat shock protein 40 in spinocerebellar ataxia type 3. PLoS ONE. 2018;13:e0201794.

    PubMed  PubMed Central  Google Scholar 

  128. Xia H, Mao Q, Eliason SL, Harper SQ, Martins IH, Orr HT, et al. RNAi suppresses polyglutamine-induced neurodegeneration in a model of spinocerebellar ataxia. Nat Med. 2004;10:816–20.

    CAS  PubMed  Google Scholar 

  129. Aleman TS, Cideciyan AV, Volpe NJ, Stevanin G, Brice A, Jacobson SG. Spinocerebellar ataxia type 7 (SCA7) shows a cone-rod dystrophy phenotype. Exp Eye Res. 2002;74:737–45.

    CAS  PubMed  Google Scholar 

  130. Sopher BL, Ladd PD, Pineda VV, Libby RT, Sunkin SM, Hurley JB, et al. CTCF regulates ataxin-7 expression through promotion of a convergently transcribed, antisense noncoding RNA. Neuron. 2011;70:1071–84.

    CAS  PubMed  PubMed Central  Google Scholar 

  131. Sparber P, Filatova A, Khantemirova M, Skoblov M. The role of long non-coding RNAs in the pathogenesis of hereditary diseases. BMC Med Genom. 2019;12:42.

    Google Scholar 

  132. Ayhan F, Perez BA, Shorrock HK, Zu T, Banez-Coronel M, Reid T, et al. SCA8 RAN polySer protein preferentially accumulates in white matter regions and is regulated by eIF3F. EMBO J. 2018;37:e99023.

    PubMed  PubMed Central  Google Scholar 

  133. Sawada J, Katayama T, Tokashiki T, Kikuchi S, Kano K, Takahashi K, et al. The first case of spinocerebellar ataxia type 8 in monozygotic twins. Intern Med. 2020;59:277–83.

    PubMed  Google Scholar 

  134. Daughters RS, Tuttle DL, Gao W, Ikeda Y, Moseley ML, Ebner TJ, et al. RNA gain-of-function in spinocerebellar ataxia type 8. PLoS Genet. 2009;5:e1000600.

    PubMed  PubMed Central  Google Scholar 

  135. Moseley ML, Zu T, Ikeda Y, Gao W, Mosemiller AK, Daughters RS, et al. Bidirectional expression of CUG and CAG expansion transcripts and intranuclear polyglutamine inclusions in spinocerebellar ataxia type 8. Nat Genet. 2006;38:758–69.

    CAS  PubMed  Google Scholar 

  136. Hardiman O, Al-Chalabi A, Chio A, Corr EM, Logroscino G, Robberecht W, et al. Amyotrophic lateral sclerosis. Nat Rev Dis Prim. 2017;3:17071.

    PubMed  Google Scholar 

  137. van Es MA, Hardiman O, Chio A, Al-Chalabi A, Pasterkamp RJ, Veldink JH, et al. Amyotrophic lateral sclerosis. Lancet. 2017;390:2084–98.

    PubMed  Google Scholar 

  138. Menzies FM, Huebener J, Renna M, Bonin M, Riess O, Rubinsztein DC. Autophagy induction reduces mutant ataxin-3 levels and toxicity in a mouse model of spinocerebellar ataxia type 3. Brain. 2010;133:93–104.

    PubMed  Google Scholar 

  139. Bond CS, Fox AH. Paraspeckles: nuclear bodies built on long noncoding RNA. J Cell Biol. 2009;186:637–44.

    CAS  PubMed  PubMed Central  Google Scholar 

  140. Nishimoto Y, Nakagawa S, Hirose T, Okano HJ, Takao M, Shibata S, et al. 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. 2013;6:31.

    CAS  PubMed  PubMed Central  Google Scholar 

  141. Corrado L, Mazzini L, Oggioni GD, Luciano B, Godi M, Brusco A, et al. ATXN-2 CAG repeat expansions are interrupted in ALS patients. Hum Genet. 2011;130:575–80.

    CAS  PubMed  Google Scholar 

  142. Toyoshima Y, Tanaka H, Shimohata M, Kimura K, Morita T, Kakita A, et al. Spinocerebellar ataxia type 2 (SCA2) is associated with TDP-43 pathology. Acta Neuropathol. 2011;122:375–8.

    PubMed  Google Scholar 

  143. Li PP, Sun X, Xia G, Arbez N, Paul S, Zhu S, et al. ATXN2-AS, a gene antisense to ATXN2, is associated with spinocerebellar ataxia type 2 and amyotrophic lateral sclerosis. Ann Neurol. 2016;80:600–15.

    CAS  PubMed  PubMed Central  Google Scholar 

  144. Balendra R, Isaacs AM. C9orf72-mediated ALS and FTD: multiple pathways to disease. Nat Rev Neurol. 2018;14:544–58.

    CAS  PubMed  PubMed Central  Google Scholar 

  145. Amick J, Ferguson SM. C9orf72: At the intersection of lysosome cell biology and neurodegenerative disease. Traffic. 2017;18:267–76.

    CAS  PubMed  PubMed Central  Google Scholar 

  146. Ling SC, Polymenidou M, Cleveland DW. Converging mechanisms in ALS and FTD: disrupted RNA and protein homeostasis. Neuron. 2013;79:416–38.

    CAS  PubMed  PubMed Central  Google Scholar 

  147. Lagier-Tourenne C, Baughn M, Rigo F, Sun S, Liu P, Li HR, et al. Targeted degradation of sense and antisense C9orf72 RNA foci as therapy for ALS and frontotemporal degeneration. Proc Natl Acad Sci USA. 2013;110:E4530–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  148. Gagliardi S, Pandini C, Garofalo M, Bordoni M, Pansarasa O, Cereda C. Long non coding RNAs and ALS: Still much to do. Noncoding RNA Res. 2018;3:226–31.

    CAS  PubMed  PubMed Central  Google Scholar 

  149. Riboldi G, Zanetta C, Ranieri M, Nizzardo M, Simone C, Magri F, et al. Antisense oligonucleotide therapy for the treatment of C9ORF72 ALS/FTD diseases. Mol Neurobiol. 2014;50:721–32.

    CAS  PubMed  Google Scholar 

  150. Smigielski L, Jagannath V, Rossler W, Walitza S, Grunblatt E. Epigenetic mechanisms in schizophrenia and other psychotic disorders: a systematic review of empirical human findings. Mol Psychiatry. 2020;25:1718–48.

    PubMed  Google Scholar 

  151. Owen MJ, Sawa A, Mortensen PB. Schizophrenia. Lancet. 2016;388:86–97.

    PubMed  PubMed Central  Google Scholar 

  152. Kesby JP, Eyles DW, McGrath JJ, Scott JG. Dopamine, psychosis and schizophrenia: the widening gap between basic and clinical neuroscience. Transl Psychiatry. 2018;8:30.

    CAS  PubMed  PubMed Central  Google Scholar 

  153. Nakata K, Lipska BK, Hyde TM, Ye T, Newburn EN, Morita Y, et al. DISC1 splice variants are upregulated in schizophrenia and associated with risk polymorphisms. Proc Natl Acad Sci USA. 2009;106:15873–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  154. Chung DW, Volk DW, Arion D, Zhang Y, Sampson AR, Lewis DA. Dysregulated ErbB4 Splicing in Schizophrenia: Selective Effects on Parvalbumin Expression. Am J Psychiatry. 2016;173:60–8.

    PubMed  Google Scholar 

  155. Barry G, Briggs JA, Vanichkina DP, Poth EM, Beveridge NJ, Ratnu VS, et al. The long non-coding RNA Gomafu is acutely regulated in response to neuronal activation and involved in schizophrenia-associated alternative splicing. Mol Psychiatry. 2014;19:486–94.

    CAS  PubMed  Google Scholar 

  156. Tsuiji H, Yoshimoto R, Hasegawa Y, Furuno M, Yoshida M, Nakagawa S. Competition between a noncoding exon and introns: Gomafu contains tandem UACUAAC repeats and associates with splicing factor-1. Genes Cells. 2011;16:479–90.

    CAS  PubMed  PubMed Central  Google Scholar 

  157. Vieta E, Berk M, Schulze TG, Carvalho AF, Suppes T, Calabrese JR, et al. Bipolar disorders. Nat Rev Dis Prim. 2018;4:18008.

    PubMed  Google Scholar 

  158. Phillips ML, Kupfer DJ. Bipolar disorder diagnosis: challenges and future directions. Lancet. 2013;381:1663–71.

    PubMed  PubMed Central  Google Scholar 

  159. Harrison PJ, Geddes JR, Tunbridge EM. The emerging neurobiology of bipolar disorder. Trends Neurosci. 2018;41:18–30.

    CAS  PubMed  PubMed Central  Google Scholar 

  160. Prisciandaro JJ, Tolliver BK, Prescot AP, Brenner HM, Renshaw PF, Brown TR, et al. Unique prefrontal GABA and glutamate disturbances in co-occurring bipolar disorder and alcohol dependence. Transl Psychiatry. 2017;7:e1163.

    CAS  PubMed  PubMed Central  Google Scholar 

  161. Ryan NM, Lihm J, Kramer M, McCarthy S, Morris SW, Arnau-Soler A, et al. DNA sequence-level analyses reveal potential phenotypic modifiers in a large family with psychiatric disorders. Mol Psychiatry. 2018;23:2254–65.

    CAS  PubMed  PubMed Central  Google Scholar 

  162. Millar JK, James R, Brandon NJ, Thomson PA. DISC1 and DISC2: discovering and dissecting molecular mechanisms underlying psychiatric illness. Ann Med. 2004;36:367–78.

    CAS  PubMed  Google Scholar 

  163. Tropea D, Hardingham N, Millar K, Fox K. Mechanisms underlying the role of DISC1 in synaptic plasticity. J Physiol. 2018;596:2747–71.

    CAS  PubMed  PubMed Central  Google Scholar 

  164. Naghavi-Gargari B, Zahirodin A, Ghaderian SMH, Shirvani-Farsani Z. Significant increasing of DISC2 long non-coding RNA expression as a potential biomarker in bipolar disorder. Neurosci Lett. 2019;696:206–11.

    CAS  PubMed  Google Scholar 

  165. Luykx JJ, Giuliani F, Giuliani G, Veldink J. Coding and non-coding RNA abnormalities in bipolar disorder. Genes 2019;10:946–60.

    CAS  PubMed Central  Google Scholar 

  166. Garcia JC, Bustos RH. The genetic diagnosis of neurodegenerative diseases and therapeutic perspectives. Brain Sci. 2018;8:222–40.

    CAS  PubMed Central  Google Scholar 

  167. Pai SI, Lin YY, Macaes B, Meneshian A, Hung CF, Wu TC. Prospects of RNA interference therapy for cancer. Gene Ther. 2006;13:464–77.

    CAS  PubMed  Google Scholar 

  168. Crooke ST, Witztum JL, Bennett CF, Baker BF. RNA-targeted therapeutics. Cell Metab. 2018;27:714–39.

    CAS  PubMed  Google Scholar 

  169. Wurster CD, Ludolph AC. Antisense oligonucleotides in neurological disorders. Ther Adv Neurol Disord. 2018;11:1756286418776932.

    PubMed  PubMed Central  Google Scholar 

  170. Buiting K, Williams C, Horsthemke B. Angelman syndrome—insights into a rare neurogenetic disorder. Nat Rev Neurol. 2016;12:584–93.

    CAS  PubMed  Google Scholar 

  171. Meng L, Ward AJ, Chun S, Bennett CF, Beaudet AL, Rigo F. Towards a therapy for Angelman syndrome by targeting a long non-coding RNA. Nature. 2015;518:409–12.

    CAS  PubMed  Google Scholar 

  172. Amodio N, Raimondi L, Juli G, Stamato MA, Caracciolo D, Tagliaferri P, et al. MALAT1: a druggable long non-coding RNA for targeted anti-cancer approaches. J Hematol Oncol. 2018;11:63.

    PubMed  PubMed Central  Google Scholar 

  173. Gutschner T, Hammerle M, Eissmann M, Hsu J, Kim Y, Hung G, et al. The noncoding RNA MALAT1 is a critical regulator of the metastasis phenotype of lung cancer cells. Cancer Res. 2013;73:1180–9.

    CAS  PubMed  Google Scholar 

  174. Zhou Y, Shan T, Ding W, Hua Z, Shen Y, Lu Z, et al. Study on mechanism about long noncoding RNA MALAT1 affecting pancreatic cancer by regulating Hippo-YAP signaling. J Cell Physiol. 2018;233:5805–14.

    CAS  PubMed  Google Scholar 

  175. Amodio N, Stamato MA, Juli G, Morelli E, Fulciniti M, Manzoni M, et al. Drugging the lncRNA MALAT1 via LNA gapmeR ASO inhibits gene expression of proteasome subunits and triggers anti-multiple myeloma activity. Leukemia. 2018;32:1948–57.

    CAS  PubMed  PubMed Central  Google Scholar 

  176. Raymond GJ, Zhao HT, Race B, Raymond LD, Williams K, Swayze EE, et al. Antisense oligonucleotides extend survival of prion-infected mice. JCI Insight. 2019;5:e131175.

    Google Scholar 

  177. Finkel RS, Mercuri E, Darras BT, Connolly AM, Kuntz NL, Kirschner J, et al. Nusinersen versus sham control in infantile-onset spinal muscular atrophy. N Engl J Med. 2017;377:1723–32.

    CAS  PubMed  Google Scholar 

  178. Talbot K, Tizzano EF. The clinical landscape for SMA in a new therapeutic era. Gene Ther. 2017;24:529–33.

    CAS  PubMed  PubMed Central  Google Scholar 

  179. Tabrizi SJ, Leavitt BR, Landwehrmeyer GB, Wild EJ, Saft C, Barker RA, et al. Targeting Huntingtin expression in patients with Huntington’s disease. N Engl J Med. 2019;380:2307–16.

    CAS  PubMed  Google Scholar 

  180. Yang H, Shang D, Xu Y, Zhang C, Feng L, Sun Z, et al. The LncRNA connectivity map: using LncRNA signatures to connect small molecules, LncRNAs, and diseases. Sci Rep. 2017;7:6655.

    PubMed  PubMed Central  Google Scholar 

  181. Yousefi H, Maheronnaghsh M, Molaei F, Mashouri L, Reza Aref A, Momeny M, et al. Long noncoding RNAs and exosomal lncRNAs: classification, and mechanisms in breast cancer metastasis and drug resistance. Oncogene. 2020;39:953–74.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by Korea Brain Research Institute (KBRI) basic research program through KBRI funded by the Ministry of Science and ICT (20-BR-02-13), and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2019R1F1A1059595). All figures were created with Biorender.com.

Author information

Author notes

  1. These authors contributed equally: Sumin Yang, Key-Hwan Lim

Authors and Affiliations

  1. Neurodegenerative Disease Research Group, Korea Brain Research Institute, Daegu, 41062, Republic of Korea

    Sumin Yang, Key-Hwan Lim, Sung-Hyun Kim & Jae-Yeol Joo

Authors
  1. Sumin Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Key-Hwan Lim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sung-Hyun Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jae-Yeol Joo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jae-Yeol Joo.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yang, S., Lim, KH., Kim, SH. et al. Molecular landscape of long noncoding RNAs in brain disorders. Mol Psychiatry 26, 1060–1074 (2021). https://doi.org/10.1038/s41380-020-00947-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41380-020-00947-5

This article is cited by

Search

Advanced search

Quick links