Roles of long noncoding RNAs in brain development, functional diversification and neurodegenerative diseases

Brain Res Bull. 2013 Aug:97:69-80. doi: 10.1016/j.brainresbull.2013.06.001. Epub 2013 Jun 10.


Long noncoding RNAs (lncRNAs) have been attracting immense research interest, while only a handful of lncRNAs have been characterized thoroughly. Their involvement in the fundamental cellular processes including regulate gene expression at epigenetics, transcription, and post-transcription highlighted a central role in cell homeostasis. However, lncRNAs studies are still at a relatively early stage, their definition, conservation, functions, and action mechanisms remain fairly complicated. Here, we give a systematic and comprehensive summary of the existing knowledge of lncRNAs in order to provide a better understanding of this new studying field. lncRNAs play important roles in brain development, neuron function and maintenance, and neurodegenerative diseases are becoming increasingly evident. In this review, we also highlighted recent studies related lncRNAs in central nervous system (CNS) development and neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS), and elucidated some specific lncRNAs which may be important for understanding the pathophysiology of neurodegenerative diseases, also have the potential as therapeutic targets.

Keywords: 5′-bromo-uridine immunoprecipitation chase followed by deep sequencing; AD; ALS; APP; Alzheimer's disease; Aβ40; Aβ42; BACE1; BC1; BC200 (BCYRN1); BDNF; BRIC–Seq; CHIRP-Seq; CNS; Ca(2+)/calmodulin-dependent protein kinase II; CaMKII; Camk2n1; DJ-1 (PARK7); DNA-binding domain protein 43; ENORs; Expression signature; FUS/TLS; GDNFOS; Gad1; Gene Nomenclature Committee; HAR1; HD; HGNCHOTAIRM1; HOX antisense intergenic RNA myeloid 1; HTTAS; HUGO; Huntingtin antisense; Huntington's disease; ISH; LRRK2; LTD; LTP; Malat1; NAT-Rad18; NO; NOSs; NTAs; Neurodegenerative disease; Neuron; Nitric oxide; Nkx2.2 AS; Nkx2.2 antisense; Noncoding RNA; Nrgn; ORF; PCG; PD; PINK1; PRC2; Parkinson disease protein 7; Parkinson's disease; RE1-silencing transcription factor/neuron-restrictive silencer factor; REST/NRSF; RIP-Chip; RNCR2; RNP immunoprecipitation-microarray; SAGE; SOX2; SRY (sex determining region Y)-box 2; Shh; Six3 opposite strand; Six3OS; Sox2 overlapping transcript; Sox2OT; TDP43TAR; TUG1; X-inactive specific transcript; Xist; amyloid precursor protein; amyloid-β-40; amyloid-β-42; amyotrophic lateral sclerosis; brain cytoplasmic RNA 1; brain derived neurotrophic factor; c-KLAN; calcium/calmodulin-dependent protein kinase II inhibitor 1; catRAPID; central nervous system; chromatin isolation by RNA purification followed by deep sequencing; combined knockdown and localization analysis of noncoding RNAs; eIF4A; eukaryotic initiation factor 4A; expressed noncoding regions; fast predictions of RNA and protein interactions and domains; fused in sarcoma/translated in liposarcoma; glial cell derived neurotrophic factor opposite strand; glutamate decarboxylase 1; human accelerated regions 1; iPSC; in situ hybridization; induced pluripotent stem cells; large intergenic noncoding RNAs; leucine-rich repeat kinase 2; lincRNAs; lncRNA; lncRNAs; long noncoding RNAs; long-term depression; long-term potentiation; metastasis-associated lung adenocarcinoma transcript 1; natural antisense RNAs; natural antisense-Rad 18; ncRNAs; neurogranin; nitric oxide synthases; noncoding RNAs; open reading frame; phosphatase and tensin homologue induced putative kinase 1; polycomb repressive complex 2; protein coding gene; retinal noncoding RNA 2; serial analysis of gene expression; sonic hedgehog; taurine upregulated gene 1; wilde type Cu/Zn superoxide dismutase; wtSOD1; β-site amyloid precursor protein-cleaving enzyme.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Brain / growth & development*
  • Brain / physiopathology*
  • Homeobox Protein Nkx-2.2
  • Homeodomain Proteins
  • Humans
  • Neurodegenerative Diseases / genetics*
  • Neurodegenerative Diseases / physiopathology
  • Nuclear Proteins
  • RNA, Long Noncoding / physiology*
  • Transcription Factors


  • Homeobox Protein Nkx-2.2
  • Homeodomain Proteins
  • NKX2-2 protein, human
  • Nuclear Proteins
  • RNA, Long Noncoding
  • Transcription Factors