MicroRNA аs targets for improving cognitive processes in neurodegenerative diseases and age-related dysfunctions

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Abstract

The study of mechanisms of cognitive functions, as well as methods of their improvement, is becoming increasingly important, since the growth of cognitive impairment is so significant that it places a heavy burden on both the patients themselves and society. Cognitive impairment includes memory loss, as well as functions involved in perception, processing/analysis of information and implementation of actions. MicroRNAs, small endogenous molecules – negative regulators of gene activity at the mRNA level, play a key role in cognitive processes and their dysfunctions. This review summarizes data on the relationship between microRNAs and cognitive processes, as well as their impairment in such socially significant diseases as Alzheimer's, Parkinson's, Huntington's and senile dementia. These diseases are currently incurable, but their course can be slowed down by supportive therapy. Difficulties are associated with the fact that clinical manifestations of these diseases appear many years after their onset. Thus, early diagnosis is necessary. The high potential of microRNAs as biomarkers for early diagnostics and the prospects for using miRNAs as targets for therapy are evidenced by a significant number of studies conducted in recent years. These studies, as well as data on the possibility of protecting cognitive impairment, including through the use of physical and mental exercises, the effect of which is mediated by microRNAs, will be analyzed in the review.

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L. N. Grinkevich

Pavlov Institute of Physiology, Russian Academy of Sciences

Author for correspondence.
Email: Larisa_Gr_spb@mail.ru
Russian Federation, Saint Petersburg, 199034

References

  1. Abuelezz N., Nasr F., Abdul Kader M., Bassiouny A., Zaky A. MicroRNAs as potential orchestrators of Alzheimer’s disease-related pathologies: Insights on current status and future possibilities // Front Aging Neurosci. 2021. V. 13. P. 743573. https://doi.org/10.3389/fnagi.2021.743573.
  2. Ai J., Sun L.H., Che H. et al. MicroRNA-195 protects against dementia induced by chronic brain hypoperfusion via its anti-amyloidogenic effect in rats // J Neurosci. 2013. V. 33. № 9. P. 3989–4001. https://doi.org/10.1523/JNEUROSCI.1997-12.2013
  3. Aksoy-Aksel A., Zampa F., Schratt G. MicroRNAs and synaptic plasticity a mutual relationship // Philos Trans R Soc Lond B Biol Sci. 2014. V. 369, № 1652. https://doi.org/10.1098/rstb.2013.0515.
  4. Alsallum M., Kaminskaya Y.P., Tsybko A.S., Kolosova N.G., Naumenko V.S. Patterns of Expression of the Key Genes of the BDNF System and Serotonin Receptors in the Brain of OXYS Rats in the Development of the Signs of Alzheimer’s Disease // Advances in Gerontology. 2024. V. 13. P. 84–93. https://doi.org/10.1134/S207905702360026X.
  5. Amber S., Zahid S. An in silico approach to identify potential downstream targets of miR-153 involved in Alzheimer's disease // Front Genet. 2024. V. 15. P. 1271404, https://pubmed.ncbi.nlm.nih.gov/38299037/doi: 10.3389/fgene.2024.1271404
  6. Andolina D. et al. MicroRNA-34 Contributes to the Stress-related Behavior and Affects 5-HT Prefrontal/GABA Amygdalar System through Regulation of Corticotropin-releasing Factor Receptor 1 // Mol Neurobiol. 2018. V. 55. № 9. P. 7401–7412. https://doi.org/10.1007/s12035-018-0925-z
  7. Antoniou A., Auderset L., Kaurani L. et al. Neuronal extracellular vesicles and associated microRNAs induce circuit connectivity downstream BDNF // Cell Rep. 2023. V. 42. № 2. P. 112063. https://doi.org/10.1016/j.celrep.2023.112063.
  8. Aquino-Jarquin G. Emerging Role of CRISPR/Cas9 Technology for MicroRNAs Editing in Cancer Research // Cancer Res. 2017. V. 77. № 24. P. 6812–6817. https://doi.org/10.1158/0008-5472.CAN-17-2142.
  9. Aten S., Hansen K.F., Snider K. et al. miR-132 couples the circadian clock to daily rhythms of neuronal plasticity and cognition // Learn Mem. 2018. V. 25. № 5. P. 214–229. 10.1101/lm.047191.117' target='_blank'>https://doi: 10.1101/lm.047191.117.
  10. Azam H.M.H., Rößling R.I., Geithe C. et al. MicroRNA biomarkers as next-generation diagnostic tools for neurodegenerative diseases: a comprehensive review // Front Mol Neurosci. 2024. V. 17. P. 1386735. https://doi.org/10.3389/fnmol.2024.1386735.
  11. Baby N., Alagappan N., Dheen S.T., Sajikumar S. MicroRNA-134-5p inhibition rescues long-term plasticity and synaptic tagging/capture in an Aβ(1-42)-induced model of Alzheimer's disease // Aging Cell. 2020. V. 19. № 1.e13046. https://doi.org/10.1111/acel.13046.
  12. Baek S., Hwan C., Kim J. Ebf3-miR218 regulation is involved in the development of dopaminergic neurons // Brain Res. 2014. V. 1587. P. 23–32. https://doi.org/10.1016/j.brainres.
  13. Barbato C., Giacovazzo G., Albiero F. et al. Cognitive Decline and Modulation of Alzhei-mer's Disease-Related Genes After Inhibition of MicroRNA-101 in Mouse Hippocampal Neurons // Mol. Neurobiol. 2020. V. 57. № 7. P. 3183–3194. https://doi.org/10.1007/s12035-020-01957-8.
  14. Benito E., Kerimoglu C., Ramachandran B. et al. RNA-Dependent Intergenerational Inheritance of Enhanced Synaptic Plasticity after Environmental Enrichment // Cell Rep. 2018. V. 23. № 2. P. 546–554. https://doi.org/10.1016/j.celrep.2018.03.059.
  15. Berger S.L. The complex language of chromatin regulation during transcription // Nature. 2007. V. 447. № 7143. P. 407–412. https://doi.org/10.1038/nature05915.
  16. Bhattacharya M., Ghosh S., Malick R.C., Patra B.C., Das B.K. Therapeutic applications of zebrafish (Danio rerio) miRNAs linked with human diseases: A prospective review // Gene. 2018. V. 679. P. 202–211. https://doi.org/10.1016/j.gene.2018.09.008.
  17. Bonk S., Kirchner K., Ameling S. et al. APOE ε4 in Depression-Associated Memory Impairment-Evidence from Genetic and MicroRNA Analyses // Biomedicines. 2022. V. 10. № 7. P. 1560. https://doi.org/10.3390/biomedicines10071560.
  18. Boukhalfa W., Jmel H., Kheriji N. et al. Decoding the genetic relationship between Alzheimer's disease and type 2 diabetes: potential risk variants and future direction for North Africa // Front Aging Neurosci. 2023. V. 15. P. 1114810. https://doi.org/10.3389/fnagi.2023.1114810.
  19. Brane A.C., Tollefsbol T.O. Targeting Telomeres and Telomerase: Studies in Aging and Disease Utilizing CRISPR/Cas9 Technology // Cells. 2019. V. 8. № 2. P. 186. https://doi.org/10.3390/cells8020186.
  20. Cai L.J., Tu L., Li T. Up-regulation of microRNA-375 ameliorates the damage of dopaminergic neurons, reduces oxidative stress and inflammation in Parkinson's disease by inhibiting SP1 // Aging (Albany NY). 2020. V. 12. № 1. P. 672–689. https://doi.org/10.18632/aging.102649.
  21. Candido S., Lupo G., Pennisi M. et al. The analysis of miRNA expression profiling datasets reveals inverse microRNA patterns in glioblastoma and Alzheimer's disease // Oncol Rep. 2019. vol. 42. № 3. P. 911–922. https://doi.org/10.3892/or.2019.7215.
  22. Cao J., Huang M., Guo L. et al. MicroRNA-195 rescues ApoE4-induced cognitive deficits and lysosomal defects in Alzheimer's disease pathogenesis // Mol Psychiatry. 2021. V. 26. № 9. P. 4687–4701. https://doi.org/10.1038/s41380-020-0824-3.
  23. Carini G., Musazzi L., Bolzetta F. et al. The Potential Role of miRNAs in Cognitive Frailty // Front Aging Neurosci. 2021. V. 13. P. 763110. https://doi.org/10.3389/fnagi.2021.763110.
  24. Cavalcante S.G., Silva C.P.N., Sola P.R. et al. ATRX-DAXX Complex Expression Levels and Telomere Length in Normal Young and Elder Autopsy Human Brains // DNA Cell Biol. 2019. V. 38. № 9. P. 955–961. https://doi.org/10.1089/dna.2019.4752.
  25. Chandran D., Krishnan S., Urulangodi M., Gopala S. Exosomal microRNAs in Parkinson's disease: Insights into biomarker potential and disease pathology // Neurol Sci. 2024. V. 45. № 8. P. 3625–3639. https://doi.org/10.1007/s10072-024-07439-2.
  26. Chen C.D., Zeldich E., Li Y., Yuste A., Abraham C.R. Activation of the Anti-Aging and Cognition-Enhancing Gene Klotho by CRISPR dCas9 Transcriptional Effector Complex // J. Mol. Neurosci. 2018. V. 64. № 2. P. 175. https://doi.org/10.1007/s12031-017-1011-0.
  27. Chen C.Y., Chao Y.M., Cho C.C. et al. Cerebral Semaphorin3D is a novel risk factor for age-associated cognitive impairment // Cell Commun Signal. 2023. V. 21. № 1. P. 140. https://doi.org/10.1186/s12964-023-01158-5.
  28. Chen J., Bai X., Wu Q. et al. Exercise Protects Against Cognitive Injury and Inflammation in Alzheimer's Disease Through Elevating miR-148a-3p // Neuroscience. 2023. V. 513. P. 126–133. https://doi.org/10.1016/j.neuroscience.2023.01.008.
  29. Chen T., Yang Y.J., Li Y.K. Chronic administration tetrahydroxystilbene glucoside promotes hippocampal memory and synaptic plasticity and activates ERKs, CaMKII and SIRT1/miR-134 in vivo // J Ethnopharmacol. 2016. V. 190. P. 74–82. https://doi.org/10.1016/j.jep.2016.06.012.
  30. Chen W., Qin C. General hallmarks of microRNAs in brain evolution and development // RNA Biol. 2015. V. 12. № 7. P. 701–708. https://doi.org/10.1080/15476286.2015.1048954.
  31. Cintado E., Tezanos P., De Las Casas M. Grandfathers-to-Grandsons Transgenerational Transmission of Exercise Positive Effects on Cognitive Performance // J Neurosci. 2024. V. 44. № 23.e2061232024. https://doi.org/10.1523/JNEUROSCI.2061-23.2024.
  32. Da Silva F.C., Rode M.P., Vietta G.G. et al. Expression levels of specific microRNAs are increased after exercise and are associated with cognitive improvement in Parkinson's disease // Mol Med Rep. 2021. V. 24. № 2. P. 618. https://doi.org/10.3892/mmr.2021.12257.
  33. Danilova A.B.; Grinkevich L.N. Failure of long-term memory formation in juvenile snails is determined by acetylation status of histone H3 and can be improved by NaB treatment // PLoS One. 2012. V. 7. № 7. e41828. https://doi.org/10.1371/journal.pone.0041828.
  34. Danka Mohammed C.P., Park J.S., Nam H.G., Kim K. MicroRNAs in brain aging // Mech Ageing Dev. 2017. V. 168. P. 3–9. https://doi.org/10.1016/j.mad.2017.01.007.
  35. De Sousa R.A.L., Improta-Caria A.C. Regulation of microRNAs in Alzheimer´s disease, type 2 diabetes, and aerobic exercise training // Metab Brain Dis. 2022. V. 37. № 3. P. 559–580. https://doi.org/10.1007/s11011-022-00903-y.
  36. Dhar P., Moodithaya S., Patil P., Adithi K. A hypothesis: MiRNA-124 mediated regulation of sirtuin 1 and vitamin D receptor gene expression accelerates aging // Aging Med (Milton). 2024. V. 7. № 3. P. 320–327. https://doi.org/10.1002/agm2.12330.
  37. Dias B.G., Ressler K.J. Amygdala-Dependent Fear Memory Consolidation via miR-34a and Notch Signaling // Neuron. 2014. V. 83. № 4. P. 906–918. https://doi.org/10.1016/j.neuron.2014.07.019.
  38. Dos Santos M.C.T., Barreto-Sanz M.A., Cor-reia B.R.S. et al. miRNA-based signatures in cerebrospinal fluid as potential diagnostic tools for early tage Parkinson’s disease // Oncotarget. 2018. V. 9. P. 17455–17465. https://doi.org/10.18632/oncotarget.24736.
  39. Dubal D.B., Yokoyama J.S., Zhu L. et al. Life extension factor klotho enhances cognition // Cell Rep. 2014. V. 7. № 4. P. 1065. https://doi.org/10.1016/j.celrep.2014.03.076.
  40. Dubnov S., Bennett E.R., Yayon N. et al. Knockout of the longevity gene Klotho perturbs aging and Alzheimer's disease-linked brain microRNAs and tRNA fragments // Commun Biol. 2024. V. 7. № 1. P. 720. https://doi.org/10.1038/s42003-024-06407-y.
  41. El-Agnaf O.M., Salem S.A., Paleologou K.E. et al. Detection of oligomeric forms of alpha-synuclein protein in human plasma as a potential biomarker for Parkinson's disease // FASEB J. 2006. V. 20. № 3. P. 419–425. https://doi.org/10.1096/fj.03-1449com.
  42. Emamzadeh F.N., Surguchov A. Parkinson's Disease: Biomarkers, Treatment, and Risk Factors // Front Neurosci. 2018. V. 12. № 612. https://doi.org/10.3389/fnins.2018.00612.
  43. Ferraldeschi M., Romano S., Giglio S. et al. Circulating hsa-miR-323b-3p in Huntington's Disease: A Pilot Study // Front Neurol. 2021. № 12. P. 657973. https://doi.org/10.3389/fneur.2021.657973.
  44. Fischer A. Epigenetic memory: the Lamarckian brain // EMBO J. 2014. V. 33. № 9. P. 945–967. https://doi.org/10.1002/embj.201387637.
  45. Gaine M.E., Chatterjee S., Abel T. Sleep Deprivation and the Epigenome // Front Neural Circuits. 2018. V. 12. P. 14. https://doi.org/10.3389/fncir.2018.00014.
  46. Gao J., Wang W.Y., Mao Y.W. et al. A novel pathway regulates memory and plasticity via SIRT1 and miR-134 // Nature. 2010. V. 466. № 7310. P. 1105–1109. https://doi.org/10.1038/nature09271.
  47. Gong Y., Zeng H., Gao S. et al., Application of CRISPR/Cas12a in miRNA-155 detection: A novel homogeneous electrochemiluminescence biosensor // Anal Chim Acta. 2024. V. 1316. № 342843. https://doi.org/10.1016/j.aca.2024.342843.
  48. Grinkevich L.N. Genome Editing and Regulation of Gene Expression Using CRISPR/Сas Technologies in Neurobiology // Uspehi Fiziol Nauk. 2021. V. 52. № 3. P. 4–23. RUS. https://doi.org/10.31857/S0301179821030024.
  49. Grinkevich L.N. The role of microRNAs in learning and long-term memory // Vavilovskii Zhurnal Genetiki i Selektsii = Vavilov Journal of Genetics and Breeding. 2020. V. 24. № 8. P. 885–896. https://doi.org/10.18699/VJ20.687.
  50. Guhathakurta S., Kim J., Adams L. et al. Targeted attenuation of elevated histone marks at SNCA alleviates α-synuclein in Parkinson's disease // EMBO Mol Med. 2021. V. 13. № 2.e12188. https://doi.org/10.15252/emmm.202012188.
  51. Han S.W., Pyun J.M., Bice P.J. et al. miR-129-5p as a biomarker for pathology and cognitive decline in Alzheimer's disease // Alzheimers Res Ther. 2024. V. 16. № 1. P. 5. https://doi.org/10.1186/s13195-023-01366-8.
  52. Han Y.P., Liu Z.J., Bao H.H., Wang Q., Su L.L. miR-126-5p Targets SP1 to Inhibit the Progression of Parkinson's Disease // Eur Neurol. 2022. V. 85. № 3. P. 235–244. https://doi.org/10.1159/000521525.
  53. Han Z., Zhang L., Ma M., Keshavarzi M. Effects of MicroRNAs and Long Non-coding RNAs on Beneficial Action of Exercise on Cognition in Degenerative Diseases: A Review // Mol Neurobiol. 2024. V. 62. № 1. P. 485–500. https://doi.org/10.1007/s12035-024-04292-4.
  54. He L., Chen Y., Lin S. et al. Regulation of Hsa-miR-4639-5p expression and its potential role in the pathogenesis of Parkinson's disease // Aging Cell. 2023. V. 22. № 6. 13840. https://doi.org/10.1111/acel.13840.
  55. Hou T.Y., Zhou Y., Zhu L.S. et al. Correcting abnormalities in miR-124/PTPN1 signaling rescues tau pathology in Alzheimer's disease // Neurochem. 2020. V. 154. № 4. P. 441–457. https://doi.org/10.1111/jnc.14961.
  56. Hu S., Wang H., Chen K. et al. MicroRNA-34c Downregulation Ameliorates Amyloid-β-Induced Synaptic Failure and Memory Deficits by Targeting VAMP2 // J Alzheimers Dis. 2015. V. 48. № 3. P. 673–686. https://doi.org/10.3233/JAD-150432.
  57. Hu Z., Li Z. miRNAs in synapse development and synaptic plasticity // Curr Opin Neurobiol. 2017. V. 45. P. 24–31. https://doi.org/10.1016/j.conb.2017.02.014. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5554733.
  58. Iqbal S., Pal D. microRNA solation, Expression Profiling, and Target Identification for Neuroprotection in Alzheimer's Disease // Methods Mol Biol. 2024. V. 2761. P. 277–290. https://doi.org/10.1007/978-1-0716-3662-6_20.
  59. Jaber V.R., Zhao Y., Sharfman N.M., Li W., Lukiw W.J. Addressing Alzheimer's Disease (AD) Neuropathology Using Anti-microRNA (AM) Strategies // Mol Neurobiol. 2019. V. 56. № 12. P. 8101–8108. https://doi.org/10.1007/s12035-019-1632-0.
  60. Jaberi K.R., Alamdari-Palangi V., Jaberi A.R. et al. The Regulation, Functions, and Signaling of miR-153 in Neurological Disorders, and Its Potential as a Biomarker and Therapeutic Target // Curr Mol Med. 2023. V. 23. № 9. P. 863–875. https://doi.org/10.2174/1566524023666220817145638.
  61. Jauhari A., Singh T., Singh P., Parmar D., Yadav S. Regulation of miR-34 Family in Neuronal Development // Mol Neurobiol. 2018. V. 55. № 2. P. 936–945. https://doi.org/ 10.1007/s12035-016-0359-4.
  62. Jawaid A., Woldemichael B.T., Kremer E.A. Memory decline and its reversal in aging and neurodegeneration involve miR-183/96/182 biogenesis // Mol Neurobiol. 2019. V. 56. № 5. P. 3451–3462. https://doi.org/10.1007/s12035-018-1314-3.
  63. Jessop P., Toledo-Rodriguez M. Hippocampal TET1 and TET2 Expression and DNA Hydroxymethylation Are Affected by Physical Exercise in Aged Mice // Front Cell Dev Biol. 2018. V. 6. P. 45. https://doi.org/10.3389/fcell.2018.00045.
  64. Ji Q., Wang X., Cai J. et al. MiR-22-3p regulates amyloid β deposit in mice model of Alzheimer's disease by targeting mitogen-activated protein kinase 14 // Curr. Neurovasc. Res. 2019. V. 16. P. 473–480. https://doi.org/10.2174/1567202616666191111124516.
  65. Jiang Y., Bian W., Chen J. et al. miRNA-137-5p improves spatial memory and cognition in Alzheimer's mice by targeting ubiquitin-specific peptidase 30 // Animal Model Exp Med. 2023. V. 6. № 6. P. 526–536. https://doi.org/10.1002/ame2.12368.
  66. Jin M., Noble J.M. What's in It for Me? Contextualizing the Potential Clinical Impacts of Lecanemab, Donanemab, and Other Anti-beta-amyloid Monoclonal Antibodies in Early Alzheimer's Disease // eNeuro. 2024. V. 11. № 9. https://doi.org/10.1523/ENEURO.0088-24.2024.
  67. John B., Enright A.J., Aravin A. et al. Human microRNA targets // PLoS Biol. 2004. V. 2. №11.e363. https://doi.org/10.1371/journal.pbio.0020363.
  68. Joo H.S., Jeon H.Y., Hong E.B., Kim H.Y., Lee J.M. Exosomes for the diagnosis and treatment of dementia // Curr Opin Psychiatry. 2023. V. 36. № 2. P. 119–125. https://doi.org/10.1097/YCO.0000000000000842.
  69. Juźwik C.A., Drake S.S., Zhang Y. et al. microRNA dysregulation in neurodegenerative diseases: A systematic review // Prog Neurobiol. 2019. V. 182. P. 101664. https://doi.org/10.1016/j.pneurobio.2019.101664.
  70. Kabaria S., Choi D.C., Chaudhuri A.D., Mouradian M.M., Junn E. Inhibition of miR-34b and miR-34c enhances alpha-synuclein expression in Parkinson's disease // FEBS Lett. 2015. V. 589. № 3. P. 319–325. https://doi.org/10.1016/j.febslet.2014.12.014.
  71. Kantor B., Tagliafierro L., Gu J., et al. Downregulation of SNCA Expression by Targeted Editing of DNA Methylation: A Potential Strategy for Precision Therapy in PD // Mol Ther. 2018. V. 26. № 11. P. 2638–2649. https://doi.org/ 10.1016/j.ymthe.2018.08.019.
  72. Karabulut S., Korkmaz Bayramov K., Bayramov R. et al. Effects of post-learning REM sleep deprivation on hippocampal plasticity-related genes and microRNA in mice // Behav Brain Res. 2019. V. 361. P. 7–13. https://doi.org/10.1016/j.bbr.2018.12.045.
  73. Karan K., Andrzejewski S., Stiles K., Hackett N., Crystal R.G. Suppression of CNS APOE4 Expression by miRNAs Delivered by the S2 AAVrh.10 Capsid-modified AAV Vector // Hum Gene Ther. 2024. V. 35. № 21–22. P. 904–916. https://doi.org/10.1089/hum.2024.112.
  74. Ke X., Huang Y., Fu Q., Lane R.H., Majnik A. Adverse Maternal Environment Alters MicroRNA-10b-5p Expression and Its Epigenetic Profile Concurrently with Impaired Hippocampal Neurogenesis in Male Mouse Hippocampus // Dev Neurosci. 2021. V. 43. № 2. P. 95–105. https://doi.org/10.1159/000515750.
  75. Kim S., Kaang B.K. Epigenetic regulation and chromatin remodeling in learning and memory // Exp Mol Med. 2017. V. 49. № 1.e281. https://doi.org/10.1038/emm.2016.140.
  76. Kołosowska K.A., Schratt G. Winterer microRNA-dependent regulation of gene expression in GABAergic interneurons // J. Front Cell Neurosci. 2023. V. 17. P. 1188574. https://doi.org/10.3389/fncel.2023.1188574.
  77. Kong E., Geng X., Wu F. et al. Microglial exosome miR-124-3p in hippocampus alleviates cognitive impairment induced by postoperative pain in elderly mice // J Cell Mol Med. 2024. V. 28. № 3.e18090. https://doi.org/10.1111/jcmm.18090.
  78. Konopka W., Kiryk A., Novak M. et al. MicroRNA loss enhances learning and memory in mice // J Neurosci. 2010. V. 30. P. 14835–14842. https://doi.org/10.1523/JNEUROSCI.3030-10.2010.
  79. Korneev S.A., Vavoulis D.V., Naskar S. et al. A CREB2-targeting microRNA is required for long-term memory after single-trial learning // Sci. Rep. 2018. V. 8. № 3950. https://doi.org/10.1038/s41598-018-22278-w.
  80. Krüger D.M., Pena-Centeno T., Liu S. et al. The plasma miRNAome in ADNI: Signatures to aid the detection of at-risk individuals // Alzheimers Dement. 2024. V. 20. № 11. P. 7479–7494. https://doi.org/10.1002/alz.14157.
  81. Kumar A., Su Y., Sharma M. et al. MicroRNA expression in extracellular vesicles as a novel blood-based biomarker for Alzheimer's // Alzheimers Dement. 2023. V. 19. № 11. P. 4952–4966. https://doi.org/10.1002/alz.13055.
  82. Kumar S., Orlov E., Gowda P. et al. Synaptosome microRNAs regulate synapse functions in Alzheimer's disease // NPJ Genom Med. 2022. V. 7. № 1. P. 47. https://doi.org/10.1038/s41525-022-00319-8.
  83. Lansdorp P.M. Sex differences in telomere length, lifespan, and embryonic dyskerin levels // Aging Cell. 2022. v. 21. № 5.e13614. https://doi.org/10.1111/acel.13614.
  84. Lee R.C., Feinbaum R.L., Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14 // Cell. 1993. V. 75. P. 843–854. https://doi.org/10.1016/0092-8674(93)90529-y.
  85. Lee S.T., Chu K., Jung K.H. et al. miR-206 regulates brain-derived neurotrophic factor in Alzheimer disease model // Ann. Neurol. 2012. V. 72. P. 269–277. https://doi.org/10.1002/ana.23588.
  86. Lepolard C., Rombaut C., Jaouen F. et al. Optimized miR-124 reporters uncover differences in miR-124 expression among neuronal populations in vitro // Front Neurosci. 2023. V. 17. P. 1257599. https://doi.org/10.3389/fnins.2023.1257599.
  87. Lesseur C., Paquette A.G., Marsit C.J. Epigenetic Regulation of Infant Neurobehavioral Outcomes // Med Epigenet. 2014. V. 2. № 2. P. 71–79. https://doi.org/10.1159/000361026.
  88. Lewis B.P., Shih I.-H., Jones-Rhoades M.W., Bartel D.P., Burge C.B. Prediction of Mam-malian MicroRNA Targets // Cell. 2003. V. 115. P. 787–798. https://doi.org/10.1016/s0092-8674(03)01018-3.
  89. Li J.Z., Ramalingam N., Li S. Targeting epigenetic mechanisms in amyloid-β-mediated Alzheimer's pathophysiology: unveiling therapeutic potential // Neural Regen Res. 2025. V. 20. № 1. P. 54–66. https://doi.org/10.4103/NRR.NRR-D-23-01827.
  90. Li Q., Wang L., Cao Y. et al. Stable Expression of dmiR-283 in the Brain Promises Positive Effects in Endurance Exercise on Sleep-Wake Behavior in Aging Drosophila // Int J Mol Sci. 2023. V. 24. № 4. P. 4180. https://doi.org/10.3390/ijms24044180.
  91. Li S., Lei Z., Sun T. The role of microRNAs in neurodegenerative diseases: a review // Cell Biol Toxicol. 2023. V. 39. № 1. P. 53–83. https://doi.org/10.1007/s10565-022-09761-x.
  92. Li T., Tao X., Sun R. et al. Cognitive-exercise dual-task intervention ameliorates cognitive decline in natural aging rats via inhibiting the promotion of LncRNA NEAT1/miR-124-3p on caveolin-1-PI3K/Akt/GSK3β Pathway // Brain Res Bull. 2023. V. 202. P. 110761. https://doi.org/10.1016/j.brainresbull.2023.110761.
  93. Li X., Zhang J., Yang Y., Wu Q., Ning H. MicroRNA-340-5p increases telomere length by targeting telomere protein POT1 to improve Alzheimer's disease in mice // Cell Biol Int. 2021. V. 45. № 6. P. 1306–1315. https://doi.org/10.1002/cbin.11576.
  94. Li Z., Chen Q., Liu J., Du Y. Physical Exercise Ameliorates the Cognitive Function and Attenuates the Neuroinflammation of Alzheimer's Disease via miR-129-5p // Dement Geriatr Cogn Disord. 2020. V. 49. № 2. P. 163–169. https://doi.org/10.1159/000507285.
  95. Lin Y.T., Seo J., Gao F. et al. APOE4 Causes Widespread Molecular and Cellular Alterations Associated with Alzheimer's Disease Phenotypes in Human iPSC-Derived Brain Cell Types // Neuron. 2018. V. 98. № 6. P. 1141. https://doi.org/10.1016/j.neuron.2018.05.008.
  96. Liu E.Y., Cali C.P., Lee E.B. RNA metabolism in neurodegenerative disease // Dis Model Mech. 2017. V. 10. № 5. P. 509–518. https://doi.org/10.1242/dmm.028613.
  97. Liu T., Li N., Pu J. et al. The plasma derived exosomal miRNA-483-5p/502-5p serve as potential MCI biomarkers in aging // Exp Gerontol. 2024. V. 186. p. 112355. https://doi.org/10.1016/j.exger.2023.112355.
  98. Liu Y., Meng X.K., Shao W.Z. et al. miR-34a/TAN1/CREB Axis Engages in Alleviating Oligodendrocyte Trophic Factor-Induced Myelin Repair Function and Astrocyte-Dependent Neuroinflammation in the Early Stages of Alzheimer's Disease: The Anti-Neurodegenerative Effect of Treadmill Exercise // Neurochem Res. 2024. V. 49. № 4. P. 1105–1120. https://doi.org/10.1007/s11064-024-04108-w.
  99. Long Y., Liu J., Wang Y., Guo H., Cui G. The complex effects of miR-146a in the pathogenesis of Alzheimer's disease // Neural Regen Res. 2025. V. 20. № 5. P. 1309–1323. https://doi.org/10.4103/NRR.NRR-D-23-01566.
  100. Lotan A., Lifschytz T., Wolf G. et al. Differential effects of chronic stress in young-adult and old female mice: cognitive-behavioral manifestations and neurobiological correlates // Mol Psychiatry. 2018. V. 23. № 6. P. 1432–1445. https://doi.org/10.1038/mp.2017.237.
  101. Lucey Brendan P., Bateman Randall J. Amyloid-β diurnal pattern: possible role of sleep in Alzheimer's disease pathogenesis // Neurobiology of Aging. 2014. V. 35. P. 29–34. https://doi.org/10.1016/j.neurobiolaging.2014.03.035.
  102. Lukiw W.J. MicroRNA (miRNA) Complexity in Alzheimer's Disease (AD) // Biology (Basel). 2023. V. 12. № 6. P. 788. https://doi.org/10.3390/biology12060788.
  103. Ma X., Zhang H., Yin H. et al. Up-regulated microRNA-218-5p ameliorates the damage of dopaminergic neurons in rats with Parkinson's disease via suppression of LASP1 // Brain Res Bull. 2021. V. 166. P. 92–101. https://doi.org/10.1016/j.brainresbull.2020.10.019.
  104. Malmevik J., Petri R., Knauff P. et al. Distinct cognitive effects and underlying transcriptome changes upon inhibition of individual miRNAs in hippocampal neurons // Sci Rep. 2016. V. 6. P. 19879. https://doi.org/ 10.1038/srep19879.
  105. Mani S., Jindal D., Singh M. Gene Therapy, A Potential Therapeutic Tool for Neurological and Neuropsychiatric Disorders: Applications, Challenges and Future Perspective // Curr Gene Ther. 2023. V. 23. № 1. P. 20–40. https://doi.org/10.2174/1566523222666220328142427.
  106. Masso A., Sanchez A., Bosch A., Gimenez-Llort L., Chillon M. Secreted alpha Klotho isoform protects against age-dependent memory deficits // Mol. Psychiatry. 2018. V. 23. № 9. P. 1937. https://doi.org/10.1038/mp.2017.211.
  107. Meccariello R., Bellenchi G.C., Pulcrano S. et al. Neuronal dysfunction and gene modulation by non-coding RNA in Parkinson's disease and synucleinopathies // Front Cell Neurosci. 2024. V. 17. P. 1328269. https://doi.org/10.3389/fncel.2023.1328269.
  108. Melas K., Talevi V., Imtiaz M.A. et al. Blood-derived microRNAs are related to cognitive domains in the general population // Alzheimers Dement. 2024. V. 20. № 10. P. 7138–7159. https://doi.org/10.1002/alz.14197.
  109. Mendes-Silva A.P., Fujimura P.T., Silva J.R.D.C. et al. Brain-enriched MicroRNA-184 is downregulated in older adults with major depressive disorder: A translational study // J Psychiatr Res. 2019. V. 111. P. 110–120. https://doi.org/10.1016/j.jpsychires.2019.01.019.
  110. Mendes-Silva A.P., Pereira K.S., Tolentino-Araujo G.T. et al. Shared Biologic Pathways Between Alzheimer Disease and Major Depression: A Systematic Review of MicroRNA Expression Studies // Am J Geriatr Psychiatry. 2016. V. 24. № 10. P. 903–912. https://doi.org/10.1016/j.jagp.2016.07.017.
  111. Miao Z., Wang Y., Sun Z. The Relationships Between Stress, Mental Disorders, and Epigenetic Regulation of BDNF // Int J Mol Sci. 2020. V. 21. № 4. P. 1375. https://doi.org/10.3390/ijms21041375.
  112. Miniarikova J., Evers M.M., Konstantinova P. Translation of MicroRNA-Based Huntingtin-Lowering Therapies from Preclinical Studies to the Clinic // Mol Ther. 2018. V. 26. № 4. P. 947–962. https://doi.org/10.1016/j.ymthe.2018.02.002.
  113. Morelli K.H., Wu Q., Gosztyla M.L. et al. An RNA-targeting CRISPR-Cas13d system alleviates disease-related phenotypes in Huntington's disease models // Nat Neurosci. 2023. V. 26. № 1. P. 27–38. https://doi.org/10.1038/s41593-022-01207-1.
  114. Muñoz-Llanos M., García-Pérez M.A., Xu X. et al. MicroRNA Profiling and Bioinformatics Target Analysis in Dorsal Hippocampus of Chronically Stressed Rats: Relevance to Depression Pathophysiology // Frontiers in Molecular Neuroscience. 2018. V. 11. № 251. https://doi.org/10.3389/fnmol.2018.00251.
  115. Niu M., Xu R., Wang J., Hou B., Xie A. MiR-133b ameliorates axon degeneration induced by MPP(+) via targeting RhoA // Neuroscience. 2016. V. 325. P. 39–49. https://doi.org/10.1016/j.neuroscience.2016.03.042.
  116. Noureddine S., Nie J., Schneider A. et al. microRNA-449a reduces growth hormone-stimulated senescent cell burden through PI3K-mTOR signaling // Proc Natl Acad Sci U S A. 2023. V. 120. № 14.e2213207120. https://doi.org/10.1073/pnas.2213207120.
  117. Paccosi E., Proietti-De-Santis L. Parkinson's Disease: From Genetics and Epigenetics to Treatment, a miRNA-Based Strategy // Int J Mol Sci. 2023. V. 24. № 11.9547. https://doi.org/10.3390/ijms24119547.
  118. Park J.S., Kim S.T., Kim S.Y. et al. A novel kit for early diagnosis of Alzheimer's disease using a fluorescent nanoparticle imaging //Sci Rep. 2019. V. 9. № 1. P. 13184. https://doi.org/10.1038/s41598-019-49711-y.
  119. Paudel B., Jeong S.Y., Martinez C.P. et al. Death Induced by Survival gene Elimination (DISE) correlates with neurotoxicity in Alzheimer's disease and aging //Nat Commun. 2024. V. 15. № 1. P. 264. https://doi.org/10.1038/s41467-023-44465-8.
  120. Pavlov K.I., Mukhin V.N., Klimenko V.M., Anisimov V.N. Telomere-telomerase system in aging, norm and pathology (literature review) // Adv Gerontol. 2017. V. 30. № 1. P. 17–26. Russian. https://pubmed.ncbi.nlm.nih.gov/28557385.
  121. Pereira J.D., Teixeira L.C.R., Mamede I. et al. miRNAs in cerebrospinal fluid associated with Alzheimer's disease: A systematic review and pathway analysis using a data mining and machine learning approach // J Neurochem. 2024. V. 168. № 6. P. 977–994. https://doi.org/10.1111/jnc.16060.
  122. Pereira R.L., Oliveira D., Pêgo A.P., Santos S.D., Moreira F.T.C. Electrochemical miRNA-34a-based biosensor for the diagnosis of Alzheimer's disease // Bioelectrochemistry. 2023. V. 154. P. 108553. https://doi.org/10.1016/j.bioelechem.
  123. Pinto-Hernandez P., Castilla-Silgado J., Coto-Vilcapoma A. et al. Modulation of microRNAs through Lifestyle Changes in Alzheimer's Disease // Nutrients. 2023. V. 15. № 17. P. 3688. https://doi.org/10.3390/nu15173688.
  124. Pulcrano S., De Gregorio R., De Sanctis C. et al. miR-218 Promotes Dopaminergic Differentiation and Controls Neuron Excitability and Neurotransmitter Release through the Regulation of a Synaptic-Related Genes Network // J Neurosci. 2023. V. 43. № 48. P. 8104–8125. https://doi.org/10.1523/JNEUROSCI.0431-23.2023.
  125. Qian H., Kang X., Hu J. et al. Reversing a model of Parkinson's disease with in situ converted nigral neurons // Nature. 2020. V. 582. № 7813. P. 550–556. https://doi.org/10.1038/s41586-020-2388-4.
  126. Qiao J., Zhao J., Chang S. et al. MicroRNA-153 improves the neurogenesis of neural stem cells and enhances the cognitive ability of aged mice through the notch signaling pathway // J. Cell Death Differ. 2020. V. 27. № 2. P. 808–825. https://doi.org/10.1038/s41418-019-0388-4.
  127. Qin Z., Han X., Ran J. et al. Exercise-Mediated Alteration of miR-192-5p Is Associated with Cognitive Improvement in Alzheimer's Disease // Neuroimmunomodulation. 2022. V. 29. № 1. P. 36–43. https://doi.org/10.1159/000516928.
  128. Rajasethupathy P., Fiumara F., Sheridan R. et al. Characterization of small RNAs in Aplysia reveals a role for miR-124 in constraining synaptic plasticity through CREB // Neuron. 2009. V. 63. № 6. P. 803–817. https://doi.org/10.1016/j.neuron.2009.05.029.
  129. Ramakrishna S., Muddashetty R.S. Emerging Role of microRNAs in Dementia // J Mol Biol. 2019. V. 431. № 9. P. 1743–1762. https://doi.org/10.1016/j.jmb.2019.01.046.
  130. Reed E.R., Latourelle J.C., Bockholt J.H. et al. MicroRNAs in CSF as prodromal biomarkers for Huntington disease in the PREDICT-HD study // Neurology. 2018. V. 90. № 4.e264–e272. https://doi.org/10.1212/WNL.0000000000004844.
  131. Ripa R., Dolfi L., Terrigno M. et al. MicroRNA miR-29 controls a compensatory response to limit neuronal iron accumulation during adult life and aging // BMC Biol. 2017. V. 15. № 1. P. 9. https://doi.org/10.1186/s12915-017-0354-x.
  132. Rivera J., Sharma B., Torres M.M., Kumar S. Factors affecting the GABAergic synapse function in Alzheimer's disease: Focus on microRNAs // Ageing Res Rev. 2023. V. 92. № 102123. https://doi.org/10.1016/j.arr.2023.102123.
  133. Sadlon A., Takousis P., Evangelou E. et al. Association of Blood MicroRNA Expression and Polymorphisms with Cognitive and Biomarker Changes in Older Adults // Prev Alzheimers Dis. 2024. V. 11. № 1. P. 230–240. https://doi.org/10.14283/jpad.2023.99.
  134. Saikia B., Dhanushkodi A. Engineered exosome therapeutics for neurodegenerative diseases // Life Sci. 2024. V. 356. № 123019. https://doi.org/10.1016/j.lfs.2024.123019.
  135. Sandau U.S., McFarland T.J., Smith S.J. et al. Differential Effects of APOE Genotype on MicroRNA Cargo of Cerebrospinal Fluid Extracellular Vesicles in Females With Alzheimer's Disease Compared to Males // Front Cell Dev Biol. 2022. V. 10. P. 864022. https://doi.org/10.3389/fcell.2022.864022.
  136. Sarkar S., Engler-Chiurazzi E.B., Cavendish J.Z. et al. Over-expression of miR-34a induces rapid cognitive impairment and Alzheimer's disease-like pathology // Brain Res. 2019. V. 1721. P. 146327. https://doi.org/10.1016/j.brainres.2019.146327.
  137. Saus E., Soria V., Escaramis G. et al. Genetic variants and abnormal processing of pre-miR-182, a circadian clock modulator, in major depression patients with late insomnia // Hum Mol Genet. 2010. V. 19. P. 4017–4025. https://doi.org/10.1093/hmg/ddq316.
  138. Sessa F., Maglietta F., Bertozzi G. et al. Human Brain Injury and miRNAs: An Experimental Study // Int J Mol Sci. 2019. V. 20. № 7. P. 1546. https://doi.org/10.3390/ijms20071546.
  139. Shafiei B., Afgar A., Nematollahi M.H., Shabani M., Nazari-Robati M. Effect of trehalose on miR-132 and SIRT1 in the hippocampus of aged rats // Neurosci Lett. 2023. V. 813. P. 137418. https://doi.org/10.1016/j.neulet.2023.137418.
  140. Shafiei B., Shabani M., Afgar A., Rajizadeh M.A., Nazari-Robati M. Trehalose Attenuates Learning and Memory Impairments in Aged Rats via Overexpression of miR-181c // Neurochem Res. 2022. V. 47. № 11. P. 3309–3317. https://doi.org/10.1007/s11064-022-03687-w.
  141. Shen J., Li Y., Qu C. et al. The enriched environment ameliorates chronic unpredictable mild stress-induced depressive-like behaviors and cognitive impairment by activating the SIRT1/miR-134 signaling pathway in hippocampus // J Affect Disord. 2019. V. 248. P. 81–90. https://doi.org/10.1016/j.jad.2019.01.031.
  142. Shi D., Han M., Liu W., Tao J., Chen L. Circulating microRNAs as diagnostic biomarkers of clinical cognitive impairment: a meta-analysis // Am. J. Alzheimers Dis. Other Dement. 2020. V. 35. № 1533317520951686. https://doi.org/10.1177/1533317520951686.
  143. Sims J.R., Zimmer J.A., Evans C.D. et al. TRAILBLAZER-ALZ 2 Investigators. Donanemab in Early Symptomatic Alzheimer Disease: The TRAILBLAZER-ALZ 2 Randomized Clinical Trial // JAMA. 2023. V. 330. № 6. P. 512–527. https://doi.org/10.1001/jama.2023.13239.
  144. Sivamaruthi B.S., Sisubalan N., Wang S., Kesika P., Chaiyasut C. Exploring the Therapeutic Potential of Green Tea (Camellia sinensis L.) in Anti-Aging Review of Mechanisms and Findings // Mini Rev Med Chem. 2024. Oct 4. https://doi.org/10.2174/0113895575331878240924035332.
  145. Smith and Kenny. MicroRNAs regulate synaptic plasticity underlying drug addiction // Genes Brain Behav. 2018. V. 17. № 3: e12424. https://doi.org/10.1111/gbb.12424
  146. Stabile F., Torromino G., Rajendran S. et al. Short-Term Memory Deficit Associates with miR-153-3p Upregulation in the Hippocampus of Middle-Aged Mice // Mol Neurobiol. 2024. V. 61. № 5. P. 3031–3041. https://doi.org/10.1007/s12035-023-03770-5.
  147. Stein C.S., McLendon J.M., Witmer N.H., Boudreau R.L. Modulation of miR-181 influences dopaminergic neuronal degeneration in a mouse model of Parkinson's disease // Mol Ther Nucleic Acids. 2022. V. 28. P. 1–15. https://doi.org/10.1016/j.omtn.2022.02.007.
  148. Sun Q., Ma L., Qiao J. et al. MiR-181a-5p promotes neural stem cell proliferation and enhances the learning and memory of aged mice // Aging Cell. 2023. V. 22. № 4.e13794. https://doi.org/10.1111/acel.13794.
  149. Talarowska M., Filip M., Szemraj J., Gałecki P. Does education level protect us from rapid ageing? Sirtuin expression versus age and level of education // Neuro Endocrinol Lett. 2019. V. 40. № 2. P. 93–98. https://pubmed.ncbi.nlm.nih.gov/31785216/
  150. Tamming R.J., Dumeaux V., Jiang Y. et al. Atrx Deletion in Neurons Leads to Sexually Dimorphic Dysregulation of miR-137 and Spatial Learning and Memory Deficits // Cell Rep. 2020. V. 31. № 13. P. 107838. https://doi.org/10.1016/j.celrep.2020.107838.
  151. Tatura R., Kraus T., Giese A. et al. Parkinson's disease: SNCA-, PARK2-, and LRRK2- targeting microRNAs elevated in cingulate gyrus // Parkinsonism Relat Disord. 2016. V. 33. P. 115–121. https://doi.org/10.1016/j.parkreldis.2016.09.028.
  152. Thomson S.B., Stam A., Brouwers C. et al. AAV5-miHTT-mediated huntingtin lowering improves brain health in a Huntington's disease mouse model // Brain. 2023. V. 146. № 6. P. 2298–2315. https://doi.org/10.1093/brain/awac458.
  153. Titze-de-Almeida R., Titze-de-Almeida S.S. miR-7 Replacement Therapy in Parkinson's Disease // Curr Gene Ther., 2018. V. 18. № 3. P. 143–153. https://doi.org/10.2174/1566523218666180430121323.
  154. Vaitkienė P., Pranckevičienė A., Radžiūnas A. et al. Association of Serum Extracellular Vesicle miRNAs with Cognitive Functioning and Quality of Life in Parkinson's Disease // Biomolecules. 2024. V. 14. № 8. P. 1000. https://doi.org/10.3390/biom14081000.
  155. Van Dyck C.H., Swanson C.J., Aisen P. et al. Lecanemab in Early Alzheimer's Disease // N Engl J Med. 2023. V. 388. № 1. P. 9–21. https://doi.org/10.1056/NEJMoa2212948.
  156. Vasiliev G.V., Ovchinnikov V.Y., Lisachev P.D., Bondar N.P., Grinkevich L.N. The Expression of miRNAs Involved in Long-Term Memory Formation in the CNS of the Mollusk Helix lucorum // Int J Mol Sci. 2023. V. 24. № 1. P. 301. https://doi.org/10.3390/ijms24010301.
  157. Veres T., Kerestély M., Kovács B.M. et al. Cellular forgetting, desensitisation, stress and ageing in signalling networks. When do cells refuse to learn more? // Cell Mol Life Sci. 2024. V. 81. № 1. P. 97. https://doi.org/10.1007/s00018-024-05112-7.
  158. Wan Z., Rasheed M., Li Y. et al. miR-218-5p and miR-320a-5p as biomarkers for brain disorders: focus on the major depressive disorder and Parkinson’s disease // Mol. Neurobiol. 2023. V. 60. № 10. P. 5642–5654. https://doi.org/10.1007/s12035-023-03391-y.
  159. Wang C.N., Wang Y.J., Wang H. et al. The Anti-dementia Effects of Donepezil Involve miR-206-3p in the Hippocampus and Cortex // Biol Pharm Bull. 2017. V. 40. № 4. P. 465–472. https://doi.org/10.1248/bpb.b16-00898.
  160. Wang J.L., Zhu X., Tang O. et al. Entropy-driven catalysis-based lateral flow assay for sensitive detection of Alzheimer 's-associated MicroRNA // Talanta. 2024. V. 271. № 125656. https://doi.org/10.1016/j.talanta.2024.125656.
  161. Wang L., Shui X., Diao Y. et al. Potential Implications of miRNAs in the Pathogenesis, Diagnosis, and Therapeutics of Alzheimer's Disease // Int J Mol Sci. 2023. V. 24. № 22. P. 16259. https://doi.org/10.3390/ijms242216259.
  162. Wang X., Liu D., Huang H.Z. et al. A Novel MicroRNA-124/PTPN1 Signal Pathway Mediates Synaptic and Memory Deficits in Alzheimer's Disease // Biol Psychiatry. 2018. V. 83. № 5. P. 395–405. https://doi.org/10.1016/j.biopsych.
  163. Wang Y., Zhao L., Kan B., Shi H., Han J. miR-22 exerts anti-Alzheimer effects via the regulation of apoptosis of hippocampal neurons // Cell. Mol. Biol. (Noisy-Le-Grand). 2018. V. 64. P. 84–89. https://pubmed.ncbi.nlm.nih.gov/30672441.
  164. Wei Z., Meng X., El Fatimy R. et al. Envi-ronmental enrichment prevents Aβ oligomer-induced synaptic dysfunction through mirna-132 and hdac3 signaling pathways // Neurobiol Dis. 2020. V. 134. № 104617. https://doi.org/10.1016/j.nbd.2019.104617.
  165. Wen Q., Wittens M.M.J., Engelborghs S. et al. Beyond CSF and Neuroimaging Assessment: Evaluating Plasma miR-145-5p as a Potential Biomarker for Mild Cognitive Impairment and Alzheimer's Disease // ACS Chem Neurosci. 2024. V. 15. № 5. P. 1042–1054. https://doi.org/10.1021/acschemneuro.3c00740.
  166. Wingo T.S., Yang J., Fan W. et al. Brain microRNAs associated with late-life depressive symptoms are also associated with cognitive trajectory and dementia // NPJ Genom Med. 2020. V. 5. P. 6. https://doi.org/10.1038/s41525-019-0113-8.
  167. Wu Y.Y., Kuo H.C. Functional roles and networks of non-coding RNAs in the pathogenesis of neurodegenerative diseases // J Biomed Sci. 2020. V. 27. № 1. P. 49. https://doi.org/10.1186/s12929-020-00636-z.
  168. Xing R., Li L., Liu X., Tian B., Cheng Y. Down regulation of miR-218, miR-124, and miR-144 relates to Parkinson’s disease via activating NF-κB signaling // Kaohsiung J Med Sci. 2020. V. 36. № 10. P. 786–792. https://doi.org/10.1002/kjm2.12241.
  169. Yang Y., Shu X., Liu D. et al. EPAC null mutation impairs learning and social interactions via aberrant regulation of miR-124 and Zif268 translation // Neuron. 2012. V. 73. № 4. P. 774–788. https://doi.org/10.1016/j.neuron.2012.02.003.
  170. Yao Y., Zhao Z., Zhang F. et al. microRNA-221 rescues the loss of dopaminergic neurons in a mouse model of Parkinson's disease // Brain Behav. 2023. V. 13. № 3.e2921. https://doi.org/10.1002/brb3.2921.
  171. Zeng C.Y., Yang T.T., Zhou H.J. et al. Lentiviral vector-mediated overexpression of Klotho in the brain improves Alzheimer's disease-like pathology and cognitive deficits in mice // Neurobiol Aging. 2019. V. 78. P. 18. https://doi.org/10.1016/j.neurobiolaging.2019.02.003.
  172. Zhang Q., Li J., Weng L. Identification and Validation of Aging-Related Genes in Alzheimer's Disease // Front Neurosci. 2022. V. 16. P. 905722. https://doi.org/10.3389/fnins.2022.905722.
  173. Zhang S., Cheng Y., Shang H. The updated development of blood-based biomarkers for Huntington's disease // J Neurol. 2023. V. 270. № 5. P. 2483–2503. https://doi.org/10.1007/s00415-023-11572-x.
  174. Zhang Y., Pang N., Huang X. et al. Ultrasound deep brain stimulation decelerates telomere shortening in Alzheimer's disease and aging mice // Fundam Res. 2022. V. 3. № 3. P. 469–478. https://doi.org/10.1016/j.fmre.2022.02.010.
  175. Zhang Y.M., Wei R.M., Zhang J.Y. et al. Resveratrol prevents cognitive deficits induced by sleep deprivation via modulating sirtuin 1 associated pathways in the hippocampus // J Biochem Mol Toxicol. 2024. V. 38. № 4.e23698. https://doi.org/10.1002/jbt.23698.
  176. Zhao Y.N., Li W.F., Li F. et al. Resveratrol improves learning and memory in normally aged mice through microRNA-CREB pathway // Biochem Biophys Res Commun. 2013. V. 435. P. 597–602. https://doi.org/10.1016/j.bbrc.2013.05.025.
  177. Zhou J., Deng K., Cheng Y. et al. CRISPR-Cas9 Based Genome Editing Reveals New Insights into MicroRNA Function and Regulation in Rice // Front Plant Sci. 2017. V. 8. № 1598. https://doi.org/10.3389/fpls.2017.01598.
  178. Zhou L.T., Liu D., Kang H.C. et al. Tau pathology epigenetically remodels the neuron-glial cross-talk in Alzheimer's disease // Sci Adv. 2023. V. 9. № 16.eabq7105. https://doi.org/10.1126/sciadv.abq7105.
  179. Zhu W., Du W., Rameshbabu A.P. et al. Targeted genome editing restores auditory function in adult mice with progressive hearing loss caused by a human microRNA mutation // Sci Transl Med. 2024. V. 16. № 755.eadn0689. https://doi.org/10.1126/scitranslmed.adn0689.
  180. Zovoilis A., Agbemenyah H.Y., Agis-Balboa R.C. et al. MicroRNA-34c is a novel target to treat dementias // EMBO J. 2011. V. 30. P. 4299–4308. https://doi.org/10.1038/emboj.2011.327.
  181. Zurawek D., Kusmider M., Faron-Gorecka A. et al. Reciprocal MicroRNA Expression in Mesocortical Circuit and Its Interplay with Serotonin Transporter Define Resilient Rats in the Chronic Mild Stress // Mol Neurobiol. 2017. V. 54. № 8. P. 5741–5751. https://doi.org/10.1007/s12035-016-0107-9.

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2. Fig. 1. Biologically active substances (BAS) used to improve age-related cognitive impairment, the mechanism of action of which is mediated by miRNA.

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3. Fig. 2. Physical and mental exercise can have a significant effect on cognitive functions. miRNAs are widely involved in these processes. Moreover, improved cognitive functions via miRNAs can be transmitted through the male line for at least two generations [14, 31].

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