Circular RNAs pp 239-243 | Cite as

Circular RNA and Alzheimer’s Disease

  • Rumana AkhterEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1087)


Circular RNAs (circRNAs) represent a special group of noncoding single-stranded highly stable ribonucleic acid entities abundant in the eukaryotic transcriptome. These circular forms of RNAs are significantly enriched in human brain and retinal tissues. However, the biological evolution and function of these circRNAs are poorly understood. Recent reports showed circRNA to be an important player in the development of neurodegenerative diseases like Alzheimer’s disease. With the progression of age, circRNA level increases in the brain and also in age-associated neurological disorder like Alzheimer’s disease (AD), Parkinson’s disease, inflammatory neuropathy, nervous system neoplasms, and prion diseases. One highly represented circRNA in the human brain and retina is a ciRS-7 (CDR1as) which acts as an endogenous, anticomplementary miRNA inhibitor or “sponge” to quench the normal functioning of miRNA-7. Low CDR1as level can lead to increase in miR-7 expression which downregulates the activity of ubiquitin protein ligase A (UBE2A), an important AD target, functionally involved in clearing toxic amyloid peptides from AD brain. This chapter focuses on the functional relationship of circRNA with AD and interplay of miRNA-mRNA-mediated genetic regulatory networks. Our conceptual understanding also suggests that circRNA can be considered as a potential biomarker and therapeutic target in AD diagnosis and treatment.


circRNA Alzheimer’s disease Amyloid CDR1as miR-7 UBE2A 


  1. 1.
    Veno MT, Hansen TB, Veno ST et al (2015) Spatio-temporal regulation of circular RNA expression during porcine embryonic brain development. Genome Biol 16:245CrossRefGoogle Scholar
  2. 2.
    You X, Vlatkovic I, Babic A et al (2015) Neural circular RNAs are derived from synaptic genes and regulated by development and plasticity. Nat Neurosci 18(4):603–610CrossRefGoogle Scholar
  3. 3.
    Rybak-Wolf A, Stottmeister C, Glazar P et al (2015) Circular RNAs in the mammalian brain are highly abundant, conserved, and dynamically expressed. Mol Cell 58(5):870–885CrossRefGoogle Scholar
  4. 4.
    Ivanov A, Memczak S, Wyler E et al (2015) Analysis of intron sequences reveals hallmarks of circular RNA biogenesis in animals. Cell Rep 10(2):170–177; Jeck WR, Sorrentino JA, Wang K et al (2013) Circular RNAs are abundant, conserved, and associated with ALU repeats. RNA 19(2):141–157CrossRefGoogle Scholar
  5. 5.
    Burnette JM, Miyamoto-Sato E, Schaub MA et al (2005) Subdivision of large introns in Drosophila by recursive splicing at nonexonic elements. Genetics 170(2):661–674CrossRefGoogle Scholar
  6. 6.
    Hardy J, Selkoe DJ (2002) The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science 297(5580):353–356CrossRefGoogle Scholar
  7. 7.
    Bertram L, Tanzi RE (2008) Thirty years of Alzheimer’s disease genetics: the implications of systematic meta-analyses. Nat Rev Neurosci 9(10):768–778CrossRefGoogle Scholar
  8. 8.
    Lukiw WJ (2013) Circular RNA (circRNA) in Alzheimer’s disease (AD). Front Genet 4:307PubMedPubMedCentralGoogle Scholar
  9. 9.
    Hansen TB, Jensen TI, Clausen BH et al (2013) Natural RNA circles function as efficient microRNA sponges. Nature 495(7441):384–388CrossRefGoogle Scholar
  10. 10.
    Cogswell JP, Ward J, Taylor IA et al (2008) Identification of miRNA changes in Alzheimer’s disease brain and CSF yields putative biomarkers and insights into disease pathways. J Alzheimers Dis 14(1):27–41CrossRefGoogle Scholar
  11. 11.
    Bingol B, Sheng M (2011) Deconstruction for reconstruction: the role of proteolysis in neural plasticity and disease. Neuron 69(1):22–32CrossRefGoogle Scholar
  12. 12.
    Lonskaya I, Shekoyan AR, Hebron ML et al (2013) Diminished parkin solubility and co-localization with intraneuronal amyloid-beta are associated with autophagic defects in Alzheimer’s disease. J Alzheimers Dis 33(1):231–247CrossRefGoogle Scholar
  13. 13.
    Ginsberg SD, Alldred MJ, Che S (2012) Gene expression levels assessed by CA1 pyramidal neuron and regional hippocampal dissections in Alzheimer’s disease. Neurobiol Dis 45(1):99–107CrossRefGoogle Scholar
  14. 14.
    Shao Y, Chen Y (2016) Roles of circular RNAs in neurologic disease. Front Mol Neurosci 9:25CrossRefGoogle Scholar
  15. 15.
    Junn E, Lee KW, Jeong BS et al (2009) Repression of alpha-synuclein expression and toxicity by microRNA-7. Proc Natl Acad Sci USA 106(31):13052–13057CrossRefGoogle Scholar
  16. 16.
    Choi DC, Chae YJ, Kabaria S et al (2014) MicroRNA-7 protects against 1-methyl-4-phenylpyridinium-induced cell death by targeting RelA. J Neurosci 34(38):12725–12737CrossRefGoogle Scholar
  17. 17.
    Chen YT, Rettig WJ, Yenamandra AK et al (1990) Cerebellar degeneration-related antigen: a highly conserved neuroectodermal marker mapped to chromosomes X in human and mouse. Proc Natl Acad Sci USA 87(8):3077–3081; Dropcho EJ, Chen YT, Posner JB et al (1987) Cloning of a brain protein identified by autoantibodies from a patient with paraneoplastic cerebellar degeneration. Proc Natl Acad Sci USA 84(13):4552–4556CrossRefGoogle Scholar
  18. 18.
    Liu Z, Jiang Z, Huang J et al (2014) miR-7 inhibits glioblastoma growth by simultaneously interfering with the PI3K/ATK and Raf/MEK/ERK pathways. Int J Oncol 44(5):1571–1580CrossRefGoogle Scholar
  19. 19.
    Wang YH, Yu XH, Luo SS et al (2015) Comprehensive circular RNA profiling reveals that circular RNA100783 is involved in chronic CD28-associated CD8(+)T cell ageing. Immun Ageing 12:17CrossRefGoogle Scholar
  20. 20.
    Fu D, Yu W, Li M et al (2015) MicroRNA-138 regulates the balance of Th1/Th2 via targeting RUNX3 in psoriasis. Immunol Lett 166(1):55–62CrossRefGoogle Scholar
  21. 21.
    Satoh J, Obayashi S, Misawa T et al (2009) Protein microarray analysis identifies human cellular prion protein interactors. Neuropathol Appl Neurobiol 35(1):16–35; Satoh J, Yamamura T (2004) Gene expression profile following stable expression of the cellular prion protein. Cell Mol Neurobiol 24(6):793–814Google Scholar
  22. 22.
    Piwecka M, Glazar P, Hernandez-Miranda LR et al (2017) Loss of a mammalian circular RNA locus causes miRNA deregulation and affects brain function. Science 357(6357)CrossRefGoogle Scholar
  23. 23.
    Guo JU, Agarwal V, Guo H et al (2014) Expanded identification and characterization of mammalian circular RNAs. Genome Biol 15(7):409CrossRefGoogle Scholar
  24. 24.
    Chen W, Schuman E (2016) Circular RNAs in brain and other tissues: a functional enigma. Trends Neurosci 39(9):597–604CrossRefGoogle Scholar

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© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.Cleveland Clinic Lerner Research InstituteClevelandUSA

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