Potential Roles of MicroRNAs in Neurodegenerative Diseases

Abstract

Neurodegenerative diseases are defined by advanced neuronal loss and can occur in hereditary or sporadic forms. As is generally known, the most common neurodegenerative diseases are Alzheimer’s disease (AD) and Parkinson’s disease (PD). Among these, AD is defined by the accumulation of beta-amyloid plaques, hyper phosphorylation of tau proteins, and chronic inflammation leading to neuronal loss. PD is related to the degeneration of dopaminergic neurons in the substantia nigra. Because of the wide heterogeneity of neurodegenerative diseases, various difficulties are encountered in diagnosing disease subtypes and developing effective treatment approaches. In recent years, microRNAs (miRNAs) have become efficient genetic biomarkers for several diseases. miRNAs regulate gene expressions post-transcriptionally and thus play a role in numerous neuronal and non-neuronal cell functions. Prior investigations have indicated the expression of miRNAs to become altered under pathological conditions, thereby suggesting that they may play a role in neurodegenerative diseases. This review focuses on the function of miRNAs in neurodegeneration and the possible contribution of altered levels of miRNAs and their target mRNAs in AD and PD patients compared to the controls shown in the previous studies. In short, altered expressions of miRNAs may play a role as potential diagnostic biomarkers with regard to neurodegenerative diseases.

Keywords

• miRNAs
• biomarker
• neurodegenerative diseases
• Alzheimer’s disease
• Parkinson’s disease

References

1. Roy B, Lee E, Li T, Rampersaud M. Role of miRNAs in neurodegeneration: from disease cause to tools of biomarker discovery and therapeutics. Genes (Basel) 2022; 13(3): 425. google scholar
2. Scheff SW, Price DA. Alzheimer’s disease-related alterations in synaptic density: neocortex and hippocampus. J Alzheimers Dis 2006; 9(3 Suppl): 101-15. google scholar
3. Ringman JM, Goate A, Masters CL, Cairns NJ, Danek A, Graff-Radford N, et al. Genetic heterogeneity in alzheimer disease and implications for treatment strategies. Curr Neurol Neurosci Rep 2014; 14(11): 499. google scholar
4. 2022 Alzheimer’s disease facts and figures. Alzheimers Dement 2022; 18(4): 700-89. google scholar
5. Marras C, Beck JC, Bower JH, Roberts E, Ritz B, Ross GW, et al. Prevalence of Parkinson’s disease across North America. NPJ Parkinson’s Disease 2018; 4(1): 1-7. google scholar
6. Ausö E, Gömez-Vicente V, Esquiva G. Biomarkers for Alzheimer’s disease early diagnosis. J Pers Med 2020; 10(3): 1-27. google scholar
7. Zubelzu M, Morera-Herreras T, Irastorza G, Gömez-Esteban JC, Murueta-Goyena A. Plasma and serum alpha-synuclein as a biomarker in Parkinson’s disease: a meta-analysis. Parkinsonism Relat Disord 2022; 99: 107-15. google scholar
8. Suwijn SR, van Boheemen CJM, de Haan RJ, Tissingh G, Booij J, de Bie RMA The diagnostic accuracy of dopamine transporter SPECT imaging to detect nigrostriatal cell loss in patients with Parkinson’s disease or clinically uncertain parkinsonism: a systematic review EJNMMI Res 2015; 5(1): 12 google scholar

9. Mayo S, Benito-Leon J, Pena-Bautista C, Baquero M, Chafer-Pericas C Recent evidence in epigenomics and proteomics biomarkers for early and minimally invasive diagnosis of Alzheimer’s and Parkinson’sdiseases.Curr Neuropharmacol 2021; 19(8): 1273-303. google scholar
10. Manna I, de Benedittis S, Quattrone A, Maisano D, Iaccino E, Quattrone A. Exosomal miRNAs as potential diagnostic biomarkers in Alzheimer’s disease. Pharmaceuticals (Basel) 2020; 13(9): 1-16. google scholar
11. Viswambharan V, Thanseem I, Vasu MM, Poovathinal SA, Anitha A. miRNAs as biomarkers of neurodegenerative disorders. Biomark Med 2017; 11(2): 151-67. google scholar
12. Idda ML, Munk R, Abdelmohsen K, Gorospe M. Noncoding RNAs in Alzheimer’s disease. Wiley Interdiscip Rev RNA 2018; 9(2): 10.1002/ wrna.1463. google scholar
13. Anglicheau D, Muthukumar T, Suthanthiran M. MicroRNAs: small RNAs with big effects. Transplantation 2010; 90(2): 105-12. google scholar
14. Bueno MJ, De Castro IP, Malumbres M. Control of cell proliferation pathways by microRNAs. Cell Cycle 2008; 7(20): 3143-8. google scholar
15. Su Z, Yang Z, Xu Y, Chen Y, Yu Q. MicroRNAs in apoptosis, autophagy and necroptosis. Oncotarget 2015; 6(11): 8474-90. google scholar
16. Leung AKL, Sharp PA. MicroRNA functions in stress responses. Mol Cell 2010; 40(2): 205-15. google scholar
17. Nowak JS, Michlewski G. miRNAs in development and pathogenesis of the nervous system. Biochem Soc Trans 2013; 41(4): 815-20. google scholar
18. Bushati N, Cohen SM. MicroRNAs in neurodegeneration. Curr Opin Neurobiol 2008; 18(3): 292-6. google scholar
19. Micheli F, Palermo R, Talora C, Ferretti E, Vacca A, Napolitano M. Regulation of proapoptotic proteins Bak1 and p53 by miR-125b in an experimental model of Alzheimer’s disease: Protective role of 170-estradiol. Neurosci Lett 2016; 629: 234-40. google scholar
20. Lee ST, Chu K, Jung KH, Kim JH, Huh JY, Yoon H, et al. miR-206 regulates brain-derived neurotrophic factor in Alzheimer disease model. Ann Neurol 2012; 72(2): 269-77. google scholar
21. Wang CN, Wang YJ, Wang H, Song L, Chen Y, Wang JL, et al. The anti-dementia effects of donepezil involve miR-206-3p in the hippocampus and cortex. Biol Pharm Bull 2017; 40(4): 465-72. google scholar
22. Li H, Yu L, Li M, Chen X, Tian Q, Jiang Y, et al. MicroRNA-150 serves as a diagnostic biomarker and is involved in the inflammatory pathogenesis of Parkinson’s disease. Mol Genet Genomic Med 2020; 8(4): e1189. google scholar
23. Zhou Y, Lu M, Du RH, Qiao C, Jiang CY, Zhang KZ, et al. MicroRNA-7 targets nod-like receptor protein 3 inflammasome to modulate neuroinflammation in the pathogenesis of Parkinson’s disease. Mol Neurodegener 2016; 11(1): 28. google scholar
24. Stein CS, McLendon JM, Witmer NH, Boudreau RL. Modulation of miR-181 influences dopaminergic neuronal degeneration in a mouse model of Parkinson’s disease. Mol Ther Nucleic Acids 2022; 28: 1-15. google scholar
25. Vahia VN. Diagnostic and statistical manual of mental disorders 5: a quick glance. Indian J Psychiatry 2013; 55(3): 220. google scholar
26. Zhao Y, Zhang Y, Zhang L, Dong Y, Ji H, Shen L. The potential markers of circulating microRNAs and long non-coding RNAs in Alzheimer’s disease. Aging Dis 2019; 10(6): 1293-301. google scholar
27. Hickman RA, Faustin A, Wisniewski T. Alzheimer Disease and its growing epidemic: risk factors, biomarkers, and the urgent need for therapeutics. Neurol Clin 2016; 34(4): 941-53. google scholar
28. Calabro M, Rinaldi C, Santoro G, Crisafulli C. The biological pathways of Alzheimer disease: a review. AIMS Neurosci 2020; 8(1): 86-132. google scholar
29. Zhao Y, Jaber V, Alexandrov PN, Vergallo A, Lista S, Hampel H, et al. microRNA-based biomarkers in Alzheimer’s disease (AD). Front Neurosci 2020; 14: 585432. google scholar
30. Yuva-Aydemir Y, Simkin A, Gascon E, Gao FB. MicroRNA-9: functional evolution of a conserved small regulatory RNA. RNA Biol 2011; 8(4): 557-64. google scholar
31. Souza VC, Morais GS, Henriques AD, Machado-Silva W, Perez DIV, Brito CJ, et al. Whole-blood levels of microRNA-9 are decreased in patients with late-onset Alzheimer Disease. Am J Alzheimers Dis Other Demen 2020; 35: 1533317520911573. google scholar
32. Yllmaz ŞG, Erdal ME, Özge AA, Sungur MA. Can peripheral microRNA expression data serve as epigenomic (upstream) biomarkers of Alzheimer’s disease? OMICS 2016; 20(8): 456-61. google scholar
33. Hebert SS, Horre K, Nicolaı L, Papadopoulou AS, Mandemakers W, Silahtaroglu AN, et al. Loss of microRNA cluster miR-29a/b-1 in sporadic Alzheimer’s disease correlates with increased BACE1/ beta-secretase expression. Proc Natl Acad Sci USA 2008; 105(17): 6415-20. google scholar
34. Gong G, An F, Wang Y, Bian M, Yu LJ, Wei C. miR-15b represses BACE1 expression in sporadic Alzheimer’s disease. Oncotarget 2017; 8(53): 91551-7. google scholar
35. Wu HZY, Thalamuthu A, Cheng L, Fowler C, Masters CL, Sachdev P, et al. Differential blood miRNA expression in brain amyloid imaging-defined Alzheimer’s disease and controls. Alzheimers Res Ther 2020; 12(1): 59. google scholar
36. Zhang M, Han W, Xu Y, Li D, Xue Q. Serum miR-128 serves as a potential diagnostic biomarker for Alzheimer’s disease. Neuropsychiatr Dis Treat 2021; 17: 269-75. google scholar
37. Geng L, Zhang T, Liu W, Chen Y. Inhibition of miR-128 abates A0-mediated cytotoxicity by targeting PPAR-y via NF-kB inactivation in primary mouse cortical neurons and Neuro2a cells. Yonsei Med J 2018; 59(9): 1096-106. google scholar
38. Balestrino R, Schapira AHV. Parkinson disease. Eur J Neurol 2020; 27(1): 27-42. google scholar
39. Ascherio A, Schwarzschild MA. The epidemiology of Parkinson’s disease: risk factors and prevention. Lancet Neurol 2016; 15(12): 1257-72. google scholar
40. Hallett PJ, Engelender S, Isacson O. Lipid and immune abnormalities causing age-dependent neurodegeneration and Parkinson’s disease. J Neuroinflammation 2019; 16(1):153 google scholar
41. Cacabelos R. Parkinson’s disease: from pathogenesis to pharmacogenomics. Int J Mol Sci 2017; 18(3): 551. google scholar
42. Wu L, Xu Q, Zhou M, Chen Y, Jiang C, Jiang Y, et al. Plasma miR-153 and miR-223 levels as potential biomarkers in Parkinson’s disease. Front Neurosci 2022; 16: 865139. google scholar
43. Yang Z, Li T, Li S, Wei M, Qi H, Shen B, et al. Altered expression levels of microRNA-132 and Nurr1 in peripheral blood of Parkinson’s disease: potential disease biomarkers. ACS Chem Neurosci 2019; 10(5): 2243-9. google scholar
44. Han L, Tang Y, Bai X, Liang X, Fan Y, Shen Y, et al. Association of the serum microRNA-29 family with cognitive impairment in Parkinson’s disease. Aging 2020; 12(13): 13518-28. google scholar
45. Guo R, Fan G, Zhang J, Wu C, Du Y, Ye H, et al. A 9-microRNA signature in serum serves as a noninvasive biomarker in early diagnosis of Alzheimer’s disease. J Alzheimer’s Dis 2017; 60(4): 1365-77. google scholar
46. Burgos K, Malenica I, Metpally R, Courtright A, Rakela B, Beach T, et al. Profiles of extracellular miRNA in cerebrospinal fluid and serum from patients with Alzheimer’s and Parkinson’s diseases correlate with disease status and features of pathology. PLoS One 2014; 9(5): e94839. google scholar
47. Khoo SK, Petillo D, Kang UJ, Resau JH, Berryhill B, Linder J, et al. Plasma-based circulating microRNA biomarkers for Parkinson’s disease. J Parkinsons Dis 2012; 2(4): 321-31. google scholar
48. He S, Huang L, Shao C, Nie T, Xia L, Cui B, et al. Several miRNAs derived from serum extracellular vesicles are potential biomarkers for early diagnosis and progression of Parkinson’s disease. Transl Neurodegener 2021; 10(1): 1-12. google scholar