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MicroRNAs in the pathophysiology of Alzheimer’s disease and Parkinson's disease: an overview

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Abstract

Neurodegenerative diseases are characterized by a progressive loss of neurons of the central nervous system (CNS) and serve as a major cause of morbidity, mortality and functional dependence especially among the elderly. Despite extensive research and development efforts, the success rate of clinical pipelines has been very limited. However, microRNAs (miRs) have been proved to be of crucial importance in regulating intracellular pathways for various pathologic conditions including those of a neurodegenerative nature. There is ample evidence of altered levels of various miRs in clinical samples of Alzheimer’s disease and Parkinson's disease patients with potentially major clinical implications. In the current review, we aim to summarize the relevant literature on the role of miRs in the pathophysiology of Alzheimer’s disease (AD) and Parkinson's disease (PD) as the two globally predominant neurodegenerative conditions.

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Abbreviations

AD:

Alzheimer’s disease

Aβ:

Amyloid-β

APP:

Amyloid precursor protein

BACE1:

Beta-site APP cleaving enzyme 1

cdk5:

Cyclin-dependent kinase-5

GSK-3:

Glycogen synthase kinase-3

MiRs:

MicroRNAs

MMPs:

Matrix metalloproteinases

ND:

Neurodegenerative diseases

Nrf2:

Nuclear factor erythroid 2-related factor 2

PD:

Parkinson's disease

RISC:

RNA-induced silencing complex

TTBK1:

Tau-tubulin kinase 1

PI3K:

Phosphatidylinositol 3-kinase

SRPK2:

Serine/threonine-protein kinase 2

SNP:

Single nucleotide polymorphism

SRPK2:

Serine/threonine-protein kinase 2

TTBK1:

Tau-tubulin kinase 1

References

  1. Erkkinen MG, Kim M-O, Geschwind MD (2018) Clinical neurology and epidemiology of the major neurodegenerative diseases. Cold Spring Harb Perspect Biol 10(4):a033118

    Article  PubMed  PubMed Central  Google Scholar 

  2. James SL et al (2018) Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 392(10159):1789–1858

    Article  Google Scholar 

  3. Cui L et al (2020) Prevalence of Alzheimer’s Disease and Parkinson’s Disease in China: An Updated Systematical Analysis. Front Aging Neurosci 12:476

    Article  Google Scholar 

  4. Jagust W (2018) Imaging the evolution and pathophysiology of Alzheimer disease. Nat Rev Neurosci 19(11):687–700

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Simon DK, Tanner CM, Brundin P (2020) Parkinson disease epidemiology, pathology, genetics, and pathophysiology. Clin Geriatr Med 36(1):1–12

    Article  PubMed  Google Scholar 

  6. de Planell-Saguer M, Rodicio MC (2011) Analytical aspects of microRNA in diagnostics: a review. Anal Chim acta 699(2):134–152

    Article  PubMed  Google Scholar 

  7. Kim VN, Nam J-W (2006) Genomics of microRNA. Trends Genet 22(3):165–173

    Article  CAS  PubMed  Google Scholar 

  8. Lau NC et al (2001) An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. Science 294(5543):858–862

    Article  CAS  PubMed  Google Scholar 

  9. Lagos-Quintana M et al (2001) Identification of novel genes coding for small expressed RNAs. Science 294(5543):853–858

    Article  CAS  PubMed  Google Scholar 

  10. Rodriguez A et al (2004) Identification of mammalian microRNA host genes and transcription units. Genome Res 14(10a):1902–1910

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Krol J, Loedige I, Filipowicz W (2010) The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet 11(9):597–610

    Article  CAS  PubMed  Google Scholar 

  12. Borchert GM, Lanier W, Davidson BL (2006) RNA polymerase III transcribes human microRNAs. Nat Struct Mol Biol 13(12):1097–1101

    Article  CAS  PubMed  Google Scholar 

  13. Lee Y et al (2004) MicroRNA genes are transcribed by RNA polymerase II. EMBO J 23(20):4051–4060

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Cai X, Hagedorn CH, Cullen BR (2004) Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs. Rna 10(12):1957–1966

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Lee Y et al (2003) The nuclear RNase III Drosha initiates microRNA processing. Nature 425(6956):415–419

    Article  CAS  PubMed  Google Scholar 

  16. Gregory RI et al (2004) The Microprocessor complex mediates the genesis of microRNAs. Nature 432(7014):235–240

    Article  CAS  PubMed  Google Scholar 

  17. Lund E et al (2004) Nuclear export of microRNA precursors. Science 303(5654):95–98

    Article  CAS  PubMed  Google Scholar 

  18. Yi R et al (2003) Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. Genes Dev 17(24):3011–3016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Bohnsack MT, Czaplinski K, Görlich D (2004) Exportin 5 is a RanGTP-dependent dsRNA-binding protein that mediates nuclear export of pre-miRNAs. Rna 10(2):185–191

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Peters L, Meister G (2007) Argonaute proteins: mediators of RNA silencing. Mol Cell 26(5):611–623

    Article  CAS  PubMed  Google Scholar 

  21. Liu X, Fortin K, Mourelatos Z (2008) MicroRNAs: biogenesis and molecular functions. Brain Pathol 18(1):113–121

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136(2):215–233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Gui Y et al (2015) Altered microRNA profiles in cerebrospinal fluid exosome in Parkinson disease and Alzheimer disease. Oncotarget 6(35):37043

    Article  PubMed  PubMed Central  Google Scholar 

  24. Brion J-P (1998) Neurofibrillary tangles and Alzheimer’s disease. Eur Neurol 40(3):130–140

    Article  CAS  PubMed  Google Scholar 

  25. Forlenza OV et al (2011) Increased platelet GSK3B activity in patients with mild cognitive impairment and Alzheimer’s disease. J Psychiatr Res 45(2):220–224

    Article  PubMed  Google Scholar 

  26. Noble W et al (2005) Inhibition of glycogen synthase kinase-3 by lithium correlates with reduced tauopathy and degeneration in vivo. Proc Natl Acad Sci 102(19):6990–6995

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Tan Z et al (2018) Nimodipine attenuates tau phosphorylation at Ser396 via miR-132/GSK-3β pathway in chronic cerebral hypoperfusion rats. Eur J Pharmacol 819:1–8

    Article  CAS  PubMed  Google Scholar 

  28. Li J et al (2019) miR-219-5p inhibits tau phosphorylation by targeting TTBK1 and GSK-3β in Alzheimer’s disease. J Cell Biochem 120(6):9936–9946

    Article  CAS  PubMed  Google Scholar 

  29. Li X-H et al (2012) AGEs induce Alzheimer-like tau pathology and memory deficit via RAGE-mediated GSK-3 activation. Neurobiol Aging 33(7):1400–1410

    Article  PubMed  Google Scholar 

  30. Ozaita A, Puighermanal E, Maldonado R (2007) Regulation of PI3K/Akt/GSK-3 pathway by cannabinoids in the brain. J Neurochem 102(4):1105–1114

    Article  CAS  PubMed  Google Scholar 

  31. Kang Q et al (2017) MiR-124-3p attenuates hyperphosphorylation of Tau protein-induced apoptosis via caveolin-1-PI3K/Akt/GSK3β pathway in N2a/APP695swe cells. Oncotarget 8(15):24314

    Article  PubMed  PubMed Central  Google Scholar 

  32. Mohamed JS, Lopez MA, Boriek AM (2010) Mechanical stretch up-regulates microRNA-26a and induces human airway smooth muscle hypertrophy by suppressing glycogen synthase kinase-3β. J Biol Chem 285(38):29336–29347

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Li B, Sun H (2013) MiR-26a promotes neurite outgrowth by repressing PTEN expression. Mol Med Rep 8(2):676–680

    Article  PubMed  Google Scholar 

  34. Santacruz K et al (2005) Tau suppression in a neurodegenerative mouse model improves memory function. Science 309(5733):476–481

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Noble W et al (2003) Cdk5 is a key factor in tau aggregation and tangle formation in vivo. Neuron 38(4):555–565

    Article  CAS  PubMed  Google Scholar 

  36. Ma X, Liu L, Meng J (2017) MicroRNA-125b promotes neurons cell apoptosis and Tau phosphorylation in Alzheimer’s disease. Neurosci Lett 661:57–62

    Article  CAS  PubMed  Google Scholar 

  37. Wang Y et al (2017) Downregulation of miR-132/212 impairs S-nitrosylation balance and induces tau phosphorylation in Alzheimer’s disease. Neurobiol Aging 51:156–166

    Article  CAS  PubMed  Google Scholar 

  38. Li C, Götz J (2017) Somatodendritic accumulation of Tau in Alzheimer’s disease is promoted by Fyn-mediated local protein translation. EMBO J 36(21):3120–3138

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Liu W, Zhao J, Lu G (2016) miR-106b inhibits tau phosphorylation at Tyr18 by targeting Fyn in a model of Alzheimer’s disease. Biochem Biophys Res Commun 478(2):852–857

    Article  CAS  PubMed  Google Scholar 

  40. Yao X et al (2020) Loss of miR-369 promotes tau phosphorylation by targeting the fyn and Serine/Threonine-protein kinase 2 signaling pathways in Alzheimer’s disease mice. Front Aging Neurosci 11:365

    Article  PubMed  PubMed Central  Google Scholar 

  41. Zhang HY et al (2008) Potential therapeutic targets of huperzine A for Alzheimer’s disease and vascular dementia. Chemico-Biol Interact 175(1–3):396–402

    Article  CAS  Google Scholar 

  42. Goodenough S, Schäfer M, Behl C (2003) Estrogen-induced cell signalling in a cellular model of Alzheimer’s disease. J Steroid Biochem Mol Biol 84(2–3):301–305

    Article  CAS  PubMed  Google Scholar 

  43. Du X et al (2017) miR-124 downregulates BACE 1 and alters autophagy in APP/PS1 transgenic mice. Toxicol Lett 280:195–205

    Article  CAS  PubMed  Google Scholar 

  44. Jash K et al (2020) MicroRNA-29b Modulates β-Secretase Activity in SH-SY5Y Cell Line and Diabetic Mouse Brain. Cell Mol Neurobiol 40(8):1367–1381

    Article  CAS  PubMed  Google Scholar 

  45. Aoyagi N et al (2010) PI3K inhibition causes the accumulation of ubiquitinated presenilin 1 without affecting the proteasome activity. Biochem Biophys Res Commun 391(2):1240–1245

    Article  CAS  PubMed  Google Scholar 

  46. Wang X et al (2014) Sorting nexin 27 regulates Aβ production through modulating γ-secretase activity. Cell Rep 9(3):1023–1033

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Liu D et al (2019) Inhibition of microRNA-155 alleviates cognitive impairment in Alzheimer’s disease and involvement of neuroinflammation. Curr Alzheimer Res 16(6):473–482

    Article  CAS  PubMed  Google Scholar 

  48. Wang X et al (2013) Loss of sorting nexin 27 contributes to excitatory synaptic dysfunction by modulating glutamate receptor recycling in Down’s syndrome. Nat Med 19(4):473–480

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Long JM et al (2019) Novel upregulation of amyloid-β precursor protein (APP) by microRNA-346 via targeting of APP mRNA 5′-untranslated region: Implications in Alzheimer’s disease. Mol Psychiatry 24(3):345–363

    Article  CAS  PubMed  Google Scholar 

  50. Liang C et al (2012) MicroRNA-153 negatively regulates the expression of amyloid precursor protein and amyloid precursor-like protein 2. Brain Res 1455:103–113

    Article  CAS  PubMed  Google Scholar 

  51. Glinsky GV (2008) An SNP-guided microRNA map of fifteen common human disorders identifies a consensus disease phenocode aiming at principal components of the nuclear import pathway. Cell Cycle 7(16):2570–2583

    Article  CAS  PubMed  Google Scholar 

  52. Cheng CM et al (2016) Up-regulation of miR-455-5p by the TGF-β–SMAD signalling axis promotes the proliferation of oral squamous cancer cells by targeting UBE2B. J Pathol 240(1):38–49

    Article  CAS  PubMed  Google Scholar 

  53. Chang JT et al (2016) Identification of MicroRNAs as breast cancer prognosis markers through the cancer genome atlas. PLoS ONE 11(12):e0168284

    Article  PubMed  PubMed Central  Google Scholar 

  54. Xi H et al (2017) hsa-miR-631 resensitizes bortezomib-resistant multiple myeloma cell lines by inhibiting UbcH10. Oncol Rep 37(2):961–968

    Article  CAS  PubMed  Google Scholar 

  55. Diomede F et al (2017) Cannabidiol modulates the expression of Alzheimer’s disease-related genes in mesenchymal stem cells. Int J Mol Sci 18(1):26

    Google Scholar 

  56. Singh BK et al (2017) Ube3a deficiency inhibits amyloid plaque formation in APPswe/PS1δE9 mouse model of Alzheimer’s disease. Hum Mol Genet 26(20):4042–4054

    Article  CAS  PubMed  Google Scholar 

  57. Song L et al (2015) miR-375 modulates radiosensitivity of HR-HPV-positive cervical cancer cells by targeting UBE3A through the p53 pathway. Med Sci Monit 21:2210

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Iwata N et al (2000) Identification of the major Aβ 1–42-degrading catabolic pathway in brain parenchyma: suppression leads to biochemical and pathological deposition. Nat Med 6(2):143–150

    Article  CAS  PubMed  Google Scholar 

  59. Zhang H et al (2017) Meta-analysis of expression and function of neprilysin in Alzheimer’s disease. Neurosci Lett 657:69–76

    Article  CAS  PubMed  Google Scholar 

  60. Chu T et al (2018) miR-26b inhibits total neurite outgrowth, promotes cells apoptosis and downregulates neprilysin in Alzheimer’s disease. Int J clin Exp Pathol 11(7):3383

    PubMed  PubMed Central  Google Scholar 

  61. Liao M-C, Van Nostrand WE (2010) Degradation of soluble and fibrillar amyloid β-protein by matrix metalloproteinase (MT1-MMP) in vitro. Biochemistry 49(6):1127–1136

    Article  CAS  PubMed  Google Scholar 

  62. Dhanavade MJ et al (2016) Molecular modeling approach to explore the role of cathepsin B from Hordeum vulgare in the degradation of Aβ peptides. Mol bioSyst 12(1):162–168

    Article  CAS  PubMed  Google Scholar 

  63. Sakamoto T et al (2006) Aluminum inhibits proteolytic degradation of amyloid β peptide by cathepsin D: a potential link between aluminum accumulation and neuritic plaque deposition. FEBS Lett 580(28–29):6543–6549

    Article  CAS  PubMed  Google Scholar 

  64. Tiribuzi R et al (2014) miR128 up-regulation correlates with impaired amyloid β (1–42) degradation in monocytes from patients with sporadic Alzheimer’s disease. Neurobiol Aging 35(2):345–356

    Article  CAS  PubMed  Google Scholar 

  65. Jin Y, Tu Q, Liu M (2018) MicroRNA-125b regulates Alzheimer’s disease through SphK1 regulation. Mol Med Rep 18(2):2373–2380

    CAS  PubMed  Google Scholar 

  66. Zhou C et al (2017) MicroRNA-144 modulates oxidative stress tolerance in SH-SY5Y cells by regulating nuclear factor erythroid 2-related factor 2-glutathione axis. Neurosci Lett 655:21–27

    Article  CAS  PubMed  Google Scholar 

  67. Wu G-D et al (2020) microRNA-592 blockade inhibits oxidative stress injury in Alzheimer’s disease astrocytes via the KIAA0319-mediated Keap1/Nrf2/ARE signaling pathway. Exp Neurol 324:113128

    Article  CAS  PubMed  Google Scholar 

  68. Duan Q, Si E (2019) MicroRNA-25 aggravates Aβ1-42-induced hippocampal neuron injury in Alzheimer’s disease by downregulating KLF2 via the Nrf2 signaling pathway in a mouse model. J Cell Biochem 120(9):15891–15905

    Article  CAS  PubMed  Google Scholar 

  69. Wong H-KA et al (2013) De-repression of FOXO3a death axis by microRNA-132 and-212 causes neuronal apoptosis in Alzheimer’s disease. Hum Mol Genet 22(15):3077–3092

    Article  CAS  PubMed  Google Scholar 

  70. Wang X et al (2009) miR-34a, a microRNA up-regulated in a double transgenic mouse model of Alzheimer’s disease, inhibits bcl2 translation. Brain Res Bull 80(4–5):268–273

    Article  CAS  PubMed  Google Scholar 

  71. Briggs CE et al (2015) Midbrain dopamine neurons in Parkinson’s disease exhibit a dysregulated miRNA and target-gene network. Brain Res 1618:111–21

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Domingo A, Klein C (2018) Genetics of Parkinson disease. Handbook of clinical neurology, vol 147. Elsevier, pp 211–227

    Google Scholar 

  73. Poewe W et al (2017) Parkinson disease. Nat Rev Dis Prim 3(1):1–21

    Google Scholar 

  74. Lashuel HA et al (2002) α-Synuclein, especially the Parkinson’s disease-associated mutants, forms pore-like annular and tubular protofibrils. J mol Biol 322(5):1089–1102

    Article  CAS  PubMed  Google Scholar 

  75. Doxakis E (2010) Post-transcriptional regulation of α-synuclein expression by mir-7 and mir-153. J Biol Chem 285(17):12726–12734

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Scherzer CR et al (2008) GATA transcription factors directly regulate the Parkinson’s disease-linked gene α-synuclein. Proc Natl Acad Sci 105(31):10907–10912

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Wright JA et al (2013) Counter-regulation of alpha-and beta-synuclein expression at the transcriptional level. Mol Cell Neurosci 57:33–41

    Article  CAS  PubMed  Google Scholar 

  78. Zhao W et al (2006) Erythropoietin stimulates phosphorylation and activation of GATA-1 via the PI3-kinase/AKT signaling pathway. Blood 107(3):907–915

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Clough RL, Dermentzaki G, Stefanis L (2009) Functional dissection of the α-synuclein promoter: transcriptional regulation by ZSCAN21 and ZNF219. J Neurochem 110(5):1479–1490

    Article  CAS  PubMed  Google Scholar 

  80. Zhang X et al (2020) Long non-coding RNA LPP-AS2 promotes glioma tumorigenesis via miR-7-5p/EGFR/PI3K/AKT/c-MYC feedback loop. J Exp Clin Cancer Res 39(1):1–20

    Article  CAS  Google Scholar 

  81. Je G, Kim Y-S (2017) Mitochondrial ROS-mediated post-transcriptional regulation of α-synuclein through miR-7 and miR-153. Neurosci Lett 661:132–136

    Article  CAS  PubMed  Google Scholar 

  82. Zimprich A et al (2004) Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron 44(4):601–607

    Article  CAS  PubMed  Google Scholar 

  83. Verma M, Steer EK, Chu CT (2014) ERKed by LRRK2: A cell biological perspective on hereditary and sporadic Parkinson's disease. Biochim Biophys Acta (BBA)-Mol Basis Dis 1842(8):1273–1281

  84. Gehrke S et al (2010) Pathogenic LRRK2 negatively regulates microRNA-mediated translational repression. Nature 466(7306):637–641

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Guerraz M, Bronstein AM (2008) Mechanisms underlying visually induced body sway. Neurosci Lett 443(1):12–16

    Article  CAS  PubMed  Google Scholar 

  86. Cho HJ et al (2013) MicroRNA-205 regulates the expression of Parkinson’s disease-related leucine-rich repeat kinase 2 protein. Hum Mol Genet 22(3):608–620

    Article  CAS  PubMed  Google Scholar 

  87. Wu Q, Xi D, Wang Y (2019) MicroRNA-599 regulates the development of Parkinson’s disease through mediating LRRK2 expression. Eur Rev Med Pharmacol Sci 23(2):724–731

    CAS  PubMed  Google Scholar 

  88. Oliveira SR et al (2021) miR-335 Targets LRRK2 and Mitigates Inflammation in Parkinson’s Disease. Front Cell Dev Biol 9:1521

    Article  Google Scholar 

  89. Xu W et al (2019) Sodium benzoate attenuates secondary brain injury by inhibiting neuronal apoptosis and reducing mitochondria-mediated oxidative stress in a rat model of intracerebral hemorrhage: Possible involvement of DJ-1/Akt/IKK/NFκB pathway. Front Mol Neurosci 12:105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Zou H et al (2015) MicroRNA-29c/PTEN pathway is involved in mice brain development and modulates neurite outgrowth in PC12 cells. Cell Mol Neurobiol 35(3):313–322

    Article  CAS  PubMed  Google Scholar 

  91. Filipczak N et al (2020) Recent advancements in liposome technology. Adv Drug Deliv Rev 156:4–22

    Article  CAS  PubMed  Google Scholar 

  92. Titze-de-Almeida R, Titze-de-Almeida SS (2018) miR-7 replacement therapy in Parkinson’s disease. Curr Gene Ther 18(3):143–153

    Article  CAS  PubMed  Google Scholar 

  93. Zhao XH et al (2019) MicroRNA-326 suppresses iNOS expression and promotes autophagy of dopaminergic neurons through the JNK signaling by targeting XBP1 in a mouse model of Parkinson’s disease. J Cell Biochem 120(9):14995–15006

    Article  CAS  PubMed  Google Scholar 

  94. Hong DS et al (2020) Phase 1 study of MRX34, a liposomal miR-34a mimic, in patients with advanced solid tumours. Br J Cancer 122(11):1630–1637

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Chen T et al (2020) Circular RNA circC3P1 restrains kidney cancer cell activity by regulating miR-21/PTEN axis and inactivating PI3K/AKT and NF-kB pathways. J Cell Physiol 235(4):4001–4010

    Article  CAS  PubMed  Google Scholar 

  96. Su C, Yang X, Lou J (2016) Geniposide reduces α-synuclein by blocking microRNA-21/lysosome-associated membrane protein 2A interaction in Parkinson disease models. Brain Res 1644:98–106

    Article  CAS  PubMed  Google Scholar 

  97. Li W et al (2018) MiR-181b regulates autophagy in a model of Parkinson’s disease by targeting the PTEN/Akt/mTOR signaling pathway. Neurosci Lett 675:83–88

    Article  CAS  PubMed  Google Scholar 

  98. Salama RM et al (2020) Neuroprotective effect of crocin against rotenone-induced Parkinson’s disease in rats: Interplay between PI3K/Akt/mTOR signaling pathway and enhanced expression of miRNA-7 and miRNA-221. Neuropharmacology 164:107900

    Article  CAS  PubMed  Google Scholar 

  99. Peng T et al (2019) Long noncoding RNA HAGLROS regulates apoptosis and autophagy in Parkinson’s disease via regulating miR-100/ATG10 axis and PI3K/Akt/mTOR pathway activation. Artif Cells Nanomed Biotechnol 47(1):2764–2774

    Article  CAS  PubMed  Google Scholar 

  100. Kim W et al (2014) miR-126 contributes to Parkinson’s disease by dysregulating the insulin-like growth factor/phosphoinositide 3-kinase signaling. Neurobiol Aging 35(7):1712–1721

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Qin X, et al. (2021) MicroRNA-185 activates PI3K/AKT signaling pathway to alleviate dopaminergic neuron damage via targeting IGF1 in Parkinson’s disease. J Drug Target 1–9

  102. Ge H et al (2019) MiR-410 exerts neuroprotective effects in a cellular model of Parkinson’s disease induced by 6-hydroxydopamine via inhibiting the PTEN/AKT/mTOR signaling pathway. Exp Mol Pathol 109:16–24

    Article  CAS  PubMed  Google Scholar 

  103. Mudo G et al (2012) Transgenic expression and activation of PGC-1α protect dopaminergic neurons in the MPTP mouse model of Parkinson’s disease. Cell Mol Life Sci 69(7):1153–1165

    Article  CAS  PubMed  Google Scholar 

  104. Mäkelä J et al (2014) Fibroblast growth factor-21 enhances mitochondrial functions and increases the activity of PGC-1α in human dopaminergic neurons via Sirtuin-1. Springerplus 3(1):1–12

    Article  Google Scholar 

  105. Wang N et al (2019) Fibroblast growth factor 21 exerts its anti-inflammatory effects on multiple cell types of adipose tissue in obesity. Obesity 27(3):399–408

    Article  CAS  PubMed  Google Scholar 

  106. Peltier J, O’Neill A, Schaffer DV (2007) PI3K/Akt and CREB regulate adult neural hippocampal progenitor proliferation and differentiation. Dev Neurobiol 67(10):1348–1361

    Article  CAS  PubMed  Google Scholar 

  107. Tu Y et al (2019) Dexmedetomidine attenuates the neurotoxicity of propofol toward primary hippocampal neurons in vitro via Erk1/2/CREB/BDNF signaling pathways. Drug Des Dev Ther 13:695

    Article  CAS  Google Scholar 

  108. Liu Z et al (2014) Ethanol suppresses PGC-1α expression by interfering with the cAMP-CREB pathway in neuronal cells. PLoS ONE 9(8):e104247

    Article  PubMed  PubMed Central  Google Scholar 

  109. Dong L et al (2020) MiR-133b inhibits MPP+-induced apoptosis in Parkinson’s disease model by inhibiting the ERK1/2 signaling pathway. Eur Rev Med Pharmacol Sci 24(21):11192–11198

    PubMed  Google Scholar 

  110. Rada P et al (2011) SCF/β-TrCP promotes glycogen synthase kinase 3-dependent degradation of the Nrf2 transcription factor in a Keap1-independent manner. Mol Cell Biol 31(6):1121–1133

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Hayes JD et al (2015) Dual regulation of transcription factor Nrf2 by Keap1 and by the combined actions of β-TrCP and GSK-3. Biochem Soc Trans 43(4):611–620

    Article  CAS  PubMed  Google Scholar 

  112. Alural B et al (2015) Lithium protects against paraquat neurotoxicity by NRF2 activation and miR-34a inhibition in SH-SY5Y cells. Front Cell Neurosci 9:209

    Article  PubMed  PubMed Central  Google Scholar 

  113. Xu X-Z et al (2019) Targeting Keap1 by miR-626 protects retinal pigment epithelium cells from oxidative injury by activating Nrf2 signaling. Free Radic Biol Med 143:387–396

    Article  CAS  PubMed  Google Scholar 

  114. Qin L-X et al (2019) Preliminary study of hsa-miR-626 change in the cerebrospinal fluid of Parkinson’s disease patients. J Clin Neurosci 70:198–201

    Article  CAS  PubMed  Google Scholar 

  115. Zhu J et al (2018) Overexpression of miR-153 promotes oxidative stress in MPP+-induced PD model by negatively regulating the Nrf2/HO-1 signaling pathway. Int J Clin Exp Pathol 11(8):4179

    CAS  PubMed  PubMed Central  Google Scholar 

  116. Blesa J et al (2015) Oxidative stress and Parkinson’s disease. Front Neuroanat 9:91

    Article  PubMed  PubMed Central  Google Scholar 

  117. Wang H-L et al. (2011) PARK6 PINK1 mutants are defective in maintaining mitochondrial membrane potential and inhibiting ROS formation of substantia nigra dopaminergic neurons. Biochim Biophys Acta (BBA)-Mol Basis Dis 1812(6):674–684

  118. Wood-Kaczmar A et al (2008) PINK1 is necessary for long term survival and mitochondrial function in human dopaminergic neurons. PLoS ONE 3(6):e2455

    Article  PubMed  PubMed Central  Google Scholar 

  119. Furlong RM et al. (2019) The Parkinson's disease gene PINK1 activates Akt via PINK1 kinase-dependent regulation of the phospholipid PI (3, 4, 5) P3. J Cell Sci 132(20):jcs233221

  120. Kim J et al (2016) miR-27a and miR-27b regulate autophagic clearance of damaged mitochondria by targeting PTEN-induced putative kinase 1 (PINK1). Mol neurodegener 11(1):1–16

    Article  Google Scholar 

  121. Lev N, Melamed E, Offen D (2003) Apoptosis and Parkinson’s disease. Prog Neuro-Psychopharmacol Biol Psychiatry 27(2):245–250

    Article  CAS  Google Scholar 

  122. Tatton WG et al (2003) Apoptosis in Parkinson’s disease: signals for neuronal degradation. Ann Neurol 53(S3):S61–S72

    Article  CAS  PubMed  Google Scholar 

  123. Sun S et al (2018) MicroRNA-212-5p prevents dopaminergic neuron death by inhibiting SIRT2 in MPTP-induced mouse model of Parkinson’s disease. Front Mol Neurosci 11:381

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Li S et al (2016) MicroRNA-7 inhibits neuronal apoptosis in a cellular Parkinson’s disease model by targeting Bax and Sirt2. Am J Transl Res 8(2):993

    CAS  PubMed  PubMed Central  Google Scholar 

  125. Gao J-X et al (2019) Overexpression of microRNA-183 promotes apoptosis of substantia nigra neurons via the inhibition of OSMR in a mouse model of Parkinson’s disease. Int J Mol Med 43(1):209–220

    CAS  PubMed  Google Scholar 

  126. Lu W et al (2020) Overexpression of MicroRNA-133a Inhibits Apoptosis and Autophagy in a Cell Model of Parkinson’s Disease by Downregulating Ras-Related C3 Botulinum Toxin Substrate 1 (RAC1). Med Sci Monit 26:e922032-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Zhu J et al (2018) Inhibition of microRNA-505 suppressed MPP+-induced cytotoxicity of SHSY5Y cells in an in vitro Parkinson’s disease model. Eur J Pharmacol 835:11–18

    Article  CAS  PubMed  Google Scholar 

  128. Dong H et al (2015) (2018) Serum microRNA profiles serve as novel biomarkers for the diagnosis of Alzheimer’s disease. Dis Mark 2015:625–659

    Google Scholar 

  129. Riancho J et al (2017) MicroRNA profile in patients with Alzheimer’s disease: analysis of miR-9-5p and miR-598 in raw and exosome enriched cerebrospinal fluid samples. J Alzheimer Dis 57(2):483–491

    Article  CAS  Google Scholar 

  130. Li F et al (2020) Profile of pathogenic proteins and microRNAs in plasma-derived extracellular vesicles in Alzheimer’s disease: a pilot study. Neuroscience 432:240–246

    Article  CAS  PubMed  Google Scholar 

  131. Gámez-Valero A et al (2019) Exploratory study on microRNA profiles from plasma-derived extracellular vesicles in Alzheimer’s disease and dementia with Lewy bodies. Transl Neurodegener 8(1):1–17

    Article  Google Scholar 

  132. McKeever PM et al (2018) MicroRNA expression levels are altered in the cerebrospinal fluid of patients with young-onset Alzheimer’s disease. Mol Neurobiol 55(12):8826–8841

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Cogswell JP et al (2008) Identification of miRNA changes in Alzheimer’s disease brain and CSF yields putative biomarkers and insights into disease pathways. J Alzheimer Dis 14(1):27–41

    Article  CAS  Google Scholar 

  134. Siedlecki-Wullich D et al (2019) Altered microRNAs related to synaptic function as potential plasma biomarkers for Alzheimer’s disease. Alzheimer Res Ther 11(1):1–11

    Article  Google Scholar 

  135. Cheng Á et al (2015) Prognostic serum miRNA biomarkers associated with Alzheimer’s disease shows concordance with neuropsychological and neuroimaging assessment. Mol Psychiatry 20(10):1188–1196

    Article  CAS  PubMed  Google Scholar 

  136. Cha DJ et al (2019) miR-212 and miR-132 are downregulated in neurally derived plasma exosomes of Alzheimer’s patients. Front Neurosci 13:1208

    Article  PubMed  PubMed Central  Google Scholar 

  137. Jash K et al (2020) MicroRNA-29b Modulates β-Secretase Activity in SH-SY5Y Cell Line and Diabetic Mouse Brain. Cell Mol Neurobiol 40(8):1367–1381

    Article  CAS  PubMed  Google Scholar 

  138. Zhu H-C et al (2012) MicroRNA-195 downregulates Alzheimer’s disease amyloid-β production by targeting BACE1. Brain Res Bull 88(6):596–601

    Article  CAS  PubMed  Google Scholar 

  139. Chopra N, et al. (2020) MicroRNA-298 reduces levels of human amyloid-β precursor protein (APP), β-site APP-converting enzyme 1 (BACE1) and specific tau protein moieties. Mol Psychiatry 1–22

  140. Du W, Lei C, Dong Y (2021) MicroRNA-149 is downregulated in Alzheimer’s disease and inhibits β-amyloid accumulation and ameliorates neuronal viability through targeting BACE1. Genet Mol Biol 44:1, e20200064

  141. Hajjari SN et al (2021) MicroRNA-4422-5p as a Negative Regulator of Amyloidogenic Secretases: A Potential Biomarker for Alzheimer’s Disease. Neuroscience 463:108–115

    Article  CAS  PubMed  Google Scholar 

  142. Chen M-L et al (2021) Inhibition of miR-331-3p and miR-9-5p ameliorates Alzheimer’s disease by enhancing autophagy. Theranostics 11(5):2395

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Gong G et al (2017) miR-15b represses BACE1 expression in sporadic Alzheimer’s disease. Oncotarget 8(53):91551

    Article  PubMed  PubMed Central  Google Scholar 

  144. Fu Y et al (2019) Intrahippocampal miR-342-3p inhibition reduces β-amyloid plaques and ameliorates learning and memory in Alzheimer’s disease. Metab Brain Dise 34(5):1355–1363

    Article  CAS  Google Scholar 

  145. Barros-Viegas AT et al (2020) miRNA-31 improves cognition and abolishes amyloid-β pathology by targeting APP and BACE1 in an animal model of alzheimer’s disease. Mol Ther-Nucleic Acids 19:1219–1236

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Kumar S, et al. (2019) Novel MicroRNA-455-3p and its protective effects against abnormal APP processing and amyloid beta toxicity in Alzheimer's disease. Biochim Biophys Acta (BBA)-Mol Basis Dis 1865(9):2428–2440

  147. Wang Y, Chang Q (2020) MicroRNA miR-212 regulates PDCD4 to attenuate Aβ 25–35-induced neurotoxicity via PI3K/AKT signaling pathway in Alzheimer’s disease. Biotechnol Lett 42:1789–1797

    Article  CAS  PubMed  Google Scholar 

  148. Wang L et al (2019) MicroRNA-200a-3p mediates neuroprotection in Alzheimer-related deficits and attenuates amyloid-beta overproduction and tau hyperphosphorylation via coregulating BACE1 and PRKACB. Front Pharmacol 10:806

    Article  PubMed  PubMed Central  Google Scholar 

  149. Fang M et al (2012) The miR-124 regulates the expression of BACE1/β-secretase correlated with cell death in Alzheimer’s disease. Toxicol Lett 209(1):94–105

    Article  CAS  PubMed  Google Scholar 

  150. Han L et al (2017) Maternally expressed gene 3 (MEG3) enhances PC12 cell hypoxia injury by targeting MiR-147. Cell Physiol Biochem 43(6):2457–2469

    Article  CAS  PubMed  Google Scholar 

  151. Fan X et al (2010) miR-20a promotes proliferation and invasion by targeting APP in human ovarian cancer cells. Acta Biochim Biophys Sin 42(5):318–324

    Article  CAS  PubMed  Google Scholar 

  152. Zhang H et al (2021) Aberrant expression of miR-148a-3p in Alzheimer’s disease and its protective role against amyloid-β induced neurotoxicity. Neurosci Lett 756:135953

    Article  CAS  PubMed  Google Scholar 

  153. Sun C et al (2020) miR-143-3p inhibition promotes neuronal survival in an Alzheimer’s disease cell model by targeting neuregulin-1. Folia Neuropathol 58(1):10–21

    Article  PubMed  Google Scholar 

  154. Bai X et al (2017) Downregulation of blood serum microRNA 29 family in patients with Parkinson’s disease. Sci Rep 7(1):1–7

    Article  Google Scholar 

  155. Botta-Orfila T et al (2014) Identification of blood serum micro-RNAs associated with idiopathic and LRRK2 Parkinson’s disease. J Neurosci Res 92(8):1071–1077

    Article  CAS  PubMed  Google Scholar 

  156. Cardo LF et al (2013) Profile of microRNAs in the plasma of Parkinson’s disease patients and healthy controls. J Neurol 260(5):1420–1422

    Article  PubMed  Google Scholar 

  157. Hoss AG et al (2016) microRNA profiles in Parkinson’s disease prefrontal cortex. Front Aging Neurosci 8:36

    Article  PubMed  PubMed Central  Google Scholar 

  158. Serafin A et al (2015) Overexpression of blood microRNAs 103a, 30b, and 29a in l-dopa–treated patients with PD. Neurology 84(7):645–653

    Article  CAS  PubMed  Google Scholar 

  159. Xie S, et al. (2020) Differential expression and significance of miRNAs in plasma extracellular vesicles of patients with Parkinson’s disease. Int J Neurosci 1–16.

  160. Tatura R et al (2016) Parkinson’s disease: SNCA-, PARK2-, and LRRK2-targeting microRNAs elevated in cingulate gyrus. Parkinsonism Relat Disord 33:115–121

    Article  PubMed  Google Scholar 

  161. Nair VD, Ge Y (2016) Alterations of miRNAs reveal a dysregulated molecular regulatory network in Parkinson’s disease striatum. Neurosci Lett 629:99–104

    Article  CAS  PubMed  Google Scholar 

  162. Zhu J et al (2021) Downregulation of microRNA-15b-5p Targeting the Akt3-Mediated GSK-3β/β-Catenin Signaling Pathway Inhibits Cell Apoptosis in Parkinson’s Disease. BioMed Res Int 2021:862–873

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran

    Mohammad Rafi Khezri, Naime Majidi Zolbanin & Morteza Ghasemnejad-Berenji

  2. Department of Molecular and Cellular Pharmacology, University of Miami-Miller School of Medicine, Miami, FL, USA

    Keyvan Yousefi

  3. Experimental and Applied Pharmaceutical Research Center, Urmia University of Medical Sciences, Urmia, Iran

    Naime Majidi Zolbanin & Morteza Ghasemnejad-Berenji

  4. Department of Pharmacology and Toxicology, School of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran

    Morteza Ghasemnejad-Berenji

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  1. Mohammad Rafi Khezri
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  2. Keyvan Yousefi
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  3. Naime Majidi Zolbanin
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  4. Morteza Ghasemnejad-Berenji
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Mohammad Rafi Khezri wrote the manuscript, and Keyvan Yousefi, Naime Majidi-Zolbanin and Morteza Ghasemnejad-Berenji edited the manuscript

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Khezri, M.R., Yousefi, K., Zolbanin, N.M. et al. MicroRNAs in the pathophysiology of Alzheimer’s disease and Parkinson's disease: an overview. Mol Neurobiol 59, 1589–1603 (2022). https://doi.org/10.1007/s12035-022-02727-4

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