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image of MicroRNAs as Biomarkers and Therapeutic Targets in Treatment-Resistant Depression: Unveiling Diagnostic and Treatment Pathways
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Abstract

Introduction

Treatment-Resistant Depression (TRD) is a complex clinical condition characterized by inadequate response to conventional antidepressant treatments. There is growing evidence that microRNAs (miRNAs) play a role in the underlying pathophysiology of TRD and may offer new avenues for diagnostics and therapy.

Methods

A structured literature review of peer-reviewed publications indexed in PubMed, Scopus, and Web of Science was conducted. The search strategy included combinations of keywords such as “treatment-resistant depression,” “microRNAs,” “biomarkers,” and “miRNA-based interventions.” Articles were selected based on relevance to miRNA expression patterns in TRD, therapeutic modulation, and their clinical potential.

Results

Dysregulation of several miRNAs including miR-135a, miR-34a, and miR-155 was consistently observed in patients with TRD. These miRNAs were linked to impaired synaptic plasticity and persistent neuroinflammation. Therapeutic approaches using miRNA mimics or inhibitors showed potential in restoring neurobiological balance and enhancing response to traditional antidepressants. However, delivery system limitations and blood-brain barrier penetration remain significant challenges.

Discussion

miRNAs appear to play a dual role in TRD, serving both as biomarkers for diagnosis and as targets for novel therapies. Integrating miRNA profiling into clinical workflows could enhance diagnostic precision and guide individualized treatment strategies. Translational barriers, such as delivery specificity and standardization of detection protocols, must be addressed before the widespread clinical application of this technology.

Conclusion

This review highlights miRNAs as promising diagnostic and therapeutic tools in TRD. Continued advancements in delivery systems and validation of biomarker panels may pave the way for their clinical implementation in personalized psychiatry.

© 2025 The Author(s). Published by Bentham Science Publishers.
This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
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References

  1. Proudman D. Greenberg P. Nellesen D. The growing burden of major depressive disorders (MDD): implications for researchers and policy makers. PharmacoEconomics 2021 39 6 619 625 10.1007/s40273‑021‑01040‑7 34013439
    [Google Scholar]
  2. The World Health Report 2001: Mental health: new understanding, new hope. World Health Organization 2001
    [Google Scholar]
  3. Neurological disorders: public health challenges. World Health Organization 2006
    [Google Scholar]
  4. Marx W. Penninx B.W.J.H. Solmi M. Furukawa T.A. Firth J. Carvalho A.F. Berk M. Major depressive disorder. Nat. Rev. Dis. Primers 2023 9 1 44 10.1038/s41572‑023‑00454‑1 37620370
    [Google Scholar]
  5. Gutiérrez-Rojas L. Porras-Segovia A. Dunne H. Andrade-González N. Cervilla J.A. Prevalence and correlates of major depressive disorder: A systematic review. Br. J. Psychiatry 2020 42 6 657 672 10.1590/1516‑4446‑2020‑0650 32756809
    [Google Scholar]
  6. Al-harbi K.S. Treatment-resistant depression: Therapeutic trends, challenges, and future directions. Patient Prefer. Adherence 2012 6 369 388 10.2147/PPA.S29716 22654508
    [Google Scholar]
  7. McIntyre R.S. Alsuwaidan M. Baune B.T. Berk M. Demyttenaere K. Goldberg J.F. Gorwood P. Ho R. Kasper S. Kennedy S.H. Ly-Uson J. Mansur R.B. McAllister-Williams R.H. Murrough J.W. Nemeroff C.B. Nierenberg A.A. Rosenblat J.D. Sanacora G. Schatzberg A.F. Shelton R. Stahl S.M. Trivedi M.H. Vieta E. Vinberg M. Williams N. Young A.H. Maj M. Treatment‐resistant depression: Definition, prevalence, detection, management, and investigational interventions. World Psychiatry 2023 22 3 394 412 10.1002/wps.21120 37713549
    [Google Scholar]
  8. Voytenko V.L. Street P. VanOrman B.T. Psychiatric comorbidities in treatment-resistant depression: Insights from a second-opinion consultation case series. Psychiatry Res. Case Rep. 2024 3 1 100205 10.1016/j.psycr.2024.100205
    [Google Scholar]
  9. Arias-de la Torre J. Vilagut G. Ronaldson A. Serrano-Blanco A. Martín V. Peters M. Valderas J.M. Dregan A. Alonso J. Prevalence and variability of current depressive disorder in 27 European countries: A population-based study. Lancet Public Health 2021 6 10 e729 e738 10.1016/S2468‑2667(21)00047‑5 33961802
    [Google Scholar]
  10. Depression and other common mental disorders: global health estimates. World Health OrganiZation 2017
    [Google Scholar]
  11. Lim G.Y. Tam W.W. Lu Y. Ho C.S. Zhang M.W. Ho R.C. Prevalence of depression in the community from 30 countries between 1994 and 2014. Sci. Rep. 2018 8 1 2861 10.1038/s41598‑018‑21243‑x 29434331
    [Google Scholar]
  12. Nemeth K. Bayraktar R. Ferracin M. Calin G.A. Non-coding RNAs in disease: From mechanisms to therapeutics. Nat. Rev. Genet. 2024 25 3 211 232 10.1038/s41576‑023‑00662‑1 37968332
    [Google Scholar]
  13. Kapranov P. Willingham A.T. Gingeras T.R. Genome-wide transcription and the implications for genomic organization. Nat. Rev. Genet. 2007 8 6 413 423 10.1038/nrg2083 17486121
    [Google Scholar]
  14. Kozomara A. Birgaoanu M. Griffiths-Jones S. miRBase: from microRNA sequences to function. Nucleic Acids Res. 2019 47 D1 D155 D162 10.1093/nar/gky1141 30423142
    [Google Scholar]
  15. Lewis B.P. Burge C.B. Bartel D.P. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 2005 120 15 20 10.1016/j.cell.2004.12.035
    [Google Scholar]
  16. Shang R. Lee S. Senavirathne G. Lai E.C. microRNAs in action: Biogenesis, function and regulation. Nat. Rev. Genet. 2023 24 12 816 833 10.1038/s41576‑023‑00611‑y 37380761
    [Google Scholar]
  17. Iacomino G. miRNAs: The road from bench to bedside. Genes 2023 14 2 314 10.3390/genes14020314 36833241
    [Google Scholar]
  18. Park S.A. Han S.M. Kim C.E. New fluid biomarkers tracking non-amyloid-β and non-tau pathology in Alzheimer’s disease. Exp. Mol. Med. 2020 52 4 556 568 10.1038/s12276‑020‑0418‑9 32284537
    [Google Scholar]
  19. Fabbri C. Hagenaars S.P. John C. Williams A.T. Shrine N. Moles L. Hanscombe K.B. Serretti A. Shepherd D.J. Free R.C. Wain L.V. Tobin M.D. Lewis C.M. Genetic and clinical characteristics of treatment-resistant depression using primary care records in two UK cohorts. Mol. Psychiatry 2021 26 7 3363 3373 10.1038/s41380‑021‑01062‑9 33753889
    [Google Scholar]
  20. Kolasa M. Faron-Górecka A. Preclinical models of treatment-resistant depression: Challenges and perspectives. Pharmacol. Rep. 2023 75 6 1326 1340 10.1007/s43440‑023‑00542‑9 37882914
    [Google Scholar]
  21. Nice U.K. Depression in adults: treatment and management. London: National Institute for Health and Care Excellence (NICE) 2022
    [Google Scholar]
  22. Kendrick T. Pilling S. Mavranezouli I. Megnin-Viggars O. Ruane C. Eadon H. Kapur N. Management of depression in adults: Summary of updated NICE guidance. BMJ 2022 378 o1557 10.1136/bmj.o1557
    [Google Scholar]
  23. Njenga C. Ramanuj P.P. de Magalhães F.J.C. Pincus H.A. New and emerging treatments for major depressive disorder. BMJ 2024 386 e073823 10.1136/bmj‑2022‑073823
    [Google Scholar]
  24. Maina G. Adami M. Ascione G. Bondi E. De Berardis D. Delmonte D. Maffezzoli S. Martinotti G. Nivoli A. Ottavianelli E. Acciavatti T. Albert U. Andreoli S. Andriola I. Romanini F.A. Bassetti R. Bettini F. Boi G. Cacciani P. Calò P. Carano A. Casolaro I. Chiappini S. Clemente P. D’Ambrosio V. d’Andrea G. Dario T. De Fazio P. de Filippis R. Di Carlo F. Di Nicola M. Di Paolo L. Di Piazza G. Di Salvo G. Fiori M. Gentile A. Lupi M. Manchia M. Marcatili M. Marchiaro L. Martiadis V. Menculini G. Migliarese G. Nappi G. Nucifora D. Olivola M. Palumbo C. Paschetta E. Pasculli E. Pessina E. Pinna F. Pinto M. Piu D. Posadinu D.G. Raffone F. Ricci V. Ritacco I. Rosso G. Simonini E. Ventriglio A. Fagiolini A. Delphi Panel Collaboration Group Nationwide consensus on the clinical management of treatment-resistant depression in Italy: a Delphi panel. Ann. Gen. Psychiatry 2023 22 1 48 10.1186/s12991‑023‑00478‑7 37996836
    [Google Scholar]
  25. Nuñez N.A. Joseph B. Pahwa M. Kumar R. Resendez M.G. Prokop L.J. Veldic M. Seshadri A. Biernacka J.M. Frye M.A. Wang Z. Singh B. Augmentation strategies for treatment resistant major depression: A systematic review and network meta-analysis. J. Affect. Disord. 2022 302 385 400 10.1016/j.jad.2021.12.134 34986373
    [Google Scholar]
  26. Almeida M.I. Reis R.M. Calin G.A. MicroRNA history: Discovery, recent applications, and next frontiers. Mutat. Res. 2011 717 1-2 1 8 10.1016/j.mrfmmm.2011.03.009 21458467
    [Google Scholar]
  27. Treiber T. Treiber N. Meister G. Regulation of microRNA biogenesis and its crosstalk with other cellular pathways. Nat. Rev. Mol. Cell Biol. 2019 20 1 5 20 10.1038/s41580‑018‑0059‑1 30228348
    [Google Scholar]
  28. Mohammadi A.H. Seyedmoalemi S. Moghanlou M. Akhlagh S.A. Talaei Zavareh S.A. Hamblin M.R. Jafari A. Mirzaei H. MicroRNAs and synaptic plasticity: From their molecular roles to response to therapy. Mol. Neurobiol. 2022 59 8 5084 5102 10.1007/s12035‑022‑02907‑2 35666404
    [Google Scholar]
  29. Gaudet A.D. Fonken L.K. Watkins L.R. Nelson R.J. Popovich P.G. MicroRNAs: Roles in regulating neuroinflammation. Neuroscientist 2018 24 3 221 245 10.1177/1073858417721150 28737113
    [Google Scholar]
  30. Nalbant E. Akkaya-Ulum Y.Z. Exploring regulatory mechanisms on miRNAs and their implications in inflammation-related diseases. Clin. Exp. Med. 2024 24 1 142 10.1007/s10238‑024‑01334‑y 38958690
    [Google Scholar]
  31. Pagano L. Rossi R. Paesano L. Marmiroli N. Marmiroli M. miRNA regulation and stress adaptation in plants. Environ. Exp. Bot. 2021 184 104369 10.1016/j.envexpbot.2020.104369
    [Google Scholar]
  32. Kucherenko M.M. Shcherbata H.R. miRNA targeting and alternative splicing in the stress response – events hosted by membrane-less compartments. J. Cell Sci. 2018 131 4 jcs202002 10.1242/jcs.202002 29444950
    [Google Scholar]
  33. Olejniczak M. Kotowska-Zimmer A. Krzyzosiak W. Stress-induced changes in miRNA biogenesis and functioning. Cell. Mol. Life Sci. 2018 75 2 177 191 10.1007/s00018‑017‑2591‑0 28717872
    [Google Scholar]
  34. Holjencin C. Jakymiw A. MicroRNAs and their big therapeutic impacts: delivery strategies for cancer intervention. Cells 2022 11 15 2332 10.3390/cells11152332 35954176
    [Google Scholar]
  35. Wang Z. Wang H. Zhou S. Mao J. Zhan Z. Duan S. miRNA interplay: Mechanisms and therapeutic interventions in cancer. MedComm Oncol. 2024 3 4 e93 10.1002/mog2.93
    [Google Scholar]
  36. Dasgupta I. Chatterjee A. Recent advances in miRNA delivery systems. Methods Protoc. 2021 4 1 10 10.3390/mps4010010 33498244
    [Google Scholar]
  37. Havlik J.L. Wahid S. Teopiz K.M. McIntyre R.S. Krystal J.H. Rhee T.G. Recent advances in the treatment of treatment-resistant depression: A narrative review of literature Published from 2018 to 2023. Curr. Psychiatry Rep. 2024 26 4 176 213 10.1007/s11920‑024‑01494‑4 38386251
    [Google Scholar]
  38. Jha M.K. Mathew S.J. Pharmacotherapies for treatment-resistant depression: How antipsychotics fit in the rapidly evolving therapeutic landscape. Am. J. Psychiatry 2023 180 3 190 199 10.1176/appi.ajp.20230025 36855876
    [Google Scholar]
  39. Appelbaum L.G. Shenasa M.A. Stolz L. Daskalakis Z. Synaptic plasticity and mental health: Methods, challenges and opportunities. Neuropsychopharmacology 2023 48 1 113 120 10.1038/s41386‑022‑01370‑w 35810199
    [Google Scholar]
  40. Abraham W.C. Jones O.D. Glanzman D.L. s plasticity of synapses the mechanism of long-term memory storage? NPJ Sci. Learning 2019 4 9 10.1038/s41539‑019‑0048‑y
    [Google Scholar]
  41. Sessa F. Maglietta F. Bertozzi G. Salerno M. Di Mizio G. Messina G. Montana A. Ricci P. Pomara C. Human brain injury and mirnas: An experimental study. Int. J. Mol. Sci. 2019 20 7 1546 10.3390/ijms20071546 30934805
    [Google Scholar]
  42. Sun Y. Gui H. Li Q. Luo Z.M. Zheng M.J. Duan J.L. Liu X. MicroRNA-124 protects neurons against apoptosis in cerebral ischemic stroke. CNS Neurosci. Ther. 2013 19 10 813 819 10.1111/cns.12142 23826665
    [Google Scholar]
  43. Ge X.T. Lei P. Wang H.C. Zhang A.L. Han Z.L. Chen X. Li S.H. Jiang R.C. Kang C.S. Zhang J.N. miR-21 improves the neurological outcome after traumatic brain injury in rats. Sci. Rep. 2014 4 1 6718 10.1038/srep06718 25342226
    [Google Scholar]
  44. Qian Y. Song J. Ouyang Y. Han Q. Chen W. Zhao X. Xie Y. Chen Y. Yuan W. Fan C. Advances in roles of miR-132 in the nervous system. Front. Pharmacol 2017 8 770 10.3389/fphar.2017.00770
    [Google Scholar]
  45. Fan W. Liang C. Ou M. Zou T. Sun F. Zhou H. Cui L. MicroRNA-146a is a wide-reaching neuroinflammatory regulator and potential treatment target in neurological diseases. Front. Mol. Neurosci. 2020 13 90 10.3389/fnmol.2020.00090 32581706
    [Google Scholar]
  46. Ghafouri-Fard S. Shoorei H. Bahroudi Z. Abak A. Majidpoor J. Taheri M. An update on the role of miR-124 in the pathogenesis of human disorders. Biomed. Pharmacother. 2021 135 111198 10.1016/j.biopha.2020.111198 33412388
    [Google Scholar]
  47. Jadhav S.P. Kamath S.P. Choolani M. Lu J. Dheen S.T. microRNA‐200b modulates microglia‐mediated neuroinflammation via the cJun/MAPK pathway. J. Neurochem. 2014 130 3 388 401 10.1111/jnc.12731 24749688
    [Google Scholar]
  48. Ma Q. Zhang L. Pearce W.J. MicroRNAs in brain development and cerebrovascular pathophysiology. Am. J. Physiol. Cell Physiol. 2019 317 1 C3 C19 10.1152/ajpcell.00022.2019 30840494
    [Google Scholar]
  49. Gao Y.N. Zhang Y.Q. Wang H. Deng Y.L. Li N.M. A new player in depression: MiRNAs as modulators of altered synaptic plasticity. Int. J. Mol. Sci. 2022 23 9 4555 10.3390/ijms23094555 35562946
    [Google Scholar]
  50. Morris G. MicroRNAs – small RNAs with a big influence on brain excitability. J. Physiol. 2023 601 10 1711 1718 10.1113/JP283719 36949604
    [Google Scholar]
  51. Cai L. Xu J. Liu J. Luo H. Yang R. Gui X. Wei L. miRNAs in treatment-resistant depression: A systematic review. Mol. Biol. Rep. 2024 51 1 638 10.1007/s11033‑024‑09554‑x 38727891
    [Google Scholar]
  52. Li L.D. Naveed M. Du Z.W. Ding H. Gu K. Wei L.L. Zhou Y.P. Meng F. Wang C. Han F. Zhou Q.G. Zhang J. Abnormal expression profile of plasma-derived exosomal microRNAs in patients with treatment-resistant depression. Hum. Genomics 2021 15 1 55 10.1186/s40246‑021‑00354‑z 34419170
    [Google Scholar]
  53. Costa A.P. Machado-Vieira R. Kaster M.P. Drugs under investigation for treatment-resistant depression. In: Managing Treatment-Resistant Depression. Elsevier 2022 493 503
    [Google Scholar]
  54. Miao C. Chang J. The important roles of microRNAs in depression: New research progress and future prospects. J. Mol. Med. (Berl.) 2021 99 5 619 636 10.1007/s00109‑021‑02052‑8 33641067
    [Google Scholar]
  55. Li Y. Tan S. Shen Y. Guo L. miR‑146a‑5p negatively regulates the IL‑1β‑stimulated inflammatory response via downregulation of the IRAK1/TRAF6 signaling pathway in human intestinal epithelial cells. Exp. Ther. Med. 2022 24 4 615 10.3892/etm.2022.11552 36160881
    [Google Scholar]
  56. Lyu B. Wei Z. Jiang L. Ma C. Yang G. Han S. MicroRNA-146a negatively regulates IL-33 in activated group 2 innate lymphoid cells by inhibiting IRAK1 and TRAF6. Genes Immun. 2020 21 1 37 44 10.1038/s41435‑019‑0084‑x 31435003
    [Google Scholar]
  57. Jiang W. Kong L. Ni Q. Lu Y. Ding W. Liu G. Pu L. Tang W. Kong L. miR-146a ameliorates liver ischemia/reperfusion injury by suppressing IRAK1 and TRAF6. PLoS One 2014 9 7 e101530 10.1371/journal.pone.0101530 24987958
    [Google Scholar]
  58. Park H. Huang X. Lu C. Cairo M.S. Zhou X. MicroRNA-146a and microRNA-146b regulate human dendritic cell apoptosis and cytokine production by targeting TRAF6 and IRAK1 proteins. J. Biol. Chem. 2015 290 5 2831 2841 10.1074/jbc.M114.591420 25505246
    [Google Scholar]
  59. Roy B. Dwivedi Y. An insight into the sprawling microverse of microRNAs in depression pathophysiology and treatment response. Neurosci. Biobehav. Rev. 2023 146 105040 10.1016/j.neubiorev.2023.105040 36639069
    [Google Scholar]
  60. Czarny P. Białek K. Ziółkowska S. Strycharz J. Barszczewska G. Sliwinski T. The importance of epigenetics in diagnostics and treatment of major depressive disorder. J. Pers. Med. 2021 11 3 167 10.3390/jpm11030167 33804455
    [Google Scholar]
  61. Karacicek B. Ceylan D. Çelik H.E.A. Genc S. Extracellular vesicles in depression. Handbook of the Biology and Pathology of Mental Disorders. Springer 2024 1 24 10.1007/978‑3‑031‑32035‑4_34‑1
    [Google Scholar]
  62. Roy B. Ochi S. Dwivedi Y. Potential of circulating miRNAs as molecular markers in mood disorders and associated suicidal behavior. Int. J. Mol. Sci. 2023 24 5 4664 10.3390/ijms24054664 36902096
    [Google Scholar]
  63. Kaur U. Chakrabarti S.S. Gambhir I. Newer insights in personalized and evidence based medicine- the role of MicroRNAs. Curr. Pharmacogenomics Person. Med. 2017 14 2 106 123 [Formerly Current Pharmacogenomics]. 10.2174/1875692115666170403101207
    [Google Scholar]
  64. Mondal P. Sarkar S. Das A. Epigenetic regulations in neurological disorders. In: Epigenetics in Organ Specific Disorders. Elsevier 2023 269 310 10.1016/B978‑0‑12‑823931‑5.00010‑4
    [Google Scholar]
  65. Hermann A. Neudert M.K. Schäfer A. Zehtner R.I. Fricke S. Seinsche R.J. Stark R. Lasting effects of cognitive emotion regulation: Neural correlates of reinterpretation and distancing. Soc. Cogn. Affect. Neurosci. 2021 16 3 268 279 10.1093/scan/nsaa159 33227135
    [Google Scholar]
  66. Cao Z. Qiu J. Yang G. Liu Y. Luo W. You L. Zheng L. Zhang T. MiR-135a biogenesis and regulation in malignancy: a new hope for cancer research and therapy. Cancer Biol. Med. 2020 17 3 569 582 10.20892/j.issn.2095‑3941.2020.0033 32944391
    [Google Scholar]
  67. Mortazavi-Jahromi S.S. Aslani M. Mirshafiey A. A comprehensive review on miR-146a molecular mechanisms in a wide spectrum of immune and non-immune inflammatory diseases. Immunol. Lett. 2020 227 8 27 10.1016/j.imlet.2020.07.008 32810557
    [Google Scholar]
  68. Abdelaal A.M. Sohal I.S. Iyer S. Sudarshan K. Kothandaraman H. Lanman N.A. Low P.S. Kasinski A.L. A first-in-class fully modified version of miR-34a with outstanding stability, activity, and anti-tumor efficacy. Oncogene 2023 42 40 2985 2999 10.1038/s41388‑023‑02801‑8 37666938
    [Google Scholar]
  69. Xu J. Zheng Y. Wang L. Liu Y. Wang X. Li Y. Chi G. miR-124: A promising therapeutic target for central nervous system injuries and diseases. Cell. Mol. Neurobiol. 2022 42 7 2031 2053 10.1007/s10571‑021‑01091‑6 33886036
    [Google Scholar]
  70. Testa U. Pelosi E. Castelli G. Labbaye C. miR-146 and miR-155: Two key modulators of immune response and tumor development. Noncoding RNA 2017 3 3 22 10.3390/ncrna3030022 29657293
    [Google Scholar]
  71. Sandoval-Bórquez A. Polakovicova I. Carrasco-Véliz N. Lobos-González L. Riquelme I. Carrasco-Avino G. Bizama C. Norero E. Owen G.I. Roa J.C. Corvalán A.H. MicroRNA-335-5p is a potential suppressor of metastasis and invasion in gastric cancer. Clin. Epigenetics 2017 9 1 114 10.1186/s13148‑017‑0413‑8 29075357
    [Google Scholar]
  72. Ardinal A.P. Wiyono A.V. Estiko R.I. Unveiling the therapeutic potential of miR ‐146a: Targeting innate inflammation in atherosclerosis. J. Cell. Mol. Med. 2024 28 19 e70121 10.1111/jcmm.70121 39392102
    [Google Scholar]
  73. Liu C.P. Zhong M. Sun J.X. He J. Gao Y. Qin F.X. miR‑146a reduces depressive behavior by inhibiting microglial activation. Mol. Med. Rep. 2021 23 6 463 10.3892/mmr.2021.12102 33880591
    [Google Scholar]
  74. Gissler M.C. Stachon P. Wolf D. Marchini T. The role of tumor necrosis factor associated factors (TRAFs) in vascular inflammation and atherosclerosis. Front. Cardiovasc. Med. 2022 9 826630 10.3389/fcvm.2022.826630 35252400
    [Google Scholar]
  75. Federico S. Pozzetti L. Papa A. Carullo G. Gemma S. Butini S. Campiani G. Relitti N. Modulation of the innate immune response by targeting toll-like receptors: A perspective on their agonists and antagonists. J. Med. Chem. 2020 63 22 13466 13513 10.1021/acs.jmedchem.0c01049 32845153
    [Google Scholar]
  76. Feinberg M.W. Moore K.J. MicroRNA regulation of atherosclerosis. Circ. Res. 2016 118 4 703 720 10.1161/CIRCRESAHA.115.306300 26892968
    [Google Scholar]
  77. Gerhardt T. Haghikia A. Stapmanns P. Leistner D.M. Immune mechanisms of plaque instability. Front. Cardiovasc. Med. 2022 8 797046 10.3389/fcvm.2021.797046 35087883
    [Google Scholar]
  78. Xiao L. Gu Y. Ren G. Chen L. Liu L. Wang X. Gao L. miRNA‐146a mimic inhibits NOX4/P38 signalling to ameliorate mouse myocardial ischaemia reperfusion (I/R) injury. Oxid. Med. Cell. Longev. 2021 2021 1 6366254 10.1155/2021/6366254 34367463
    [Google Scholar]
  79. Hendgen-Cotta U.B. Messiha D. Esfeld S. Deenen R. Rassaf T. Totzeck M. Inorganic nitrite modulates miRNA signatures in acute myocardial in vivo ischemia/reperfusion. Free Radic. Res. 2017 51 1 91 102 10.1080/10715762.2017.1282158 28090786
    [Google Scholar]
  80. Fan C. Li Y. Lan T. Wang W. Long Y. Yu S.Y. Microglia secrete miR-146a-5p-containing exosomes to regulate neurogenesis in depression. Mol. Ther. 2022 30 3 1300 1314 10.1016/j.ymthe.2021.11.006 34768001
    [Google Scholar]
  81. Brites D. Fernandes A. Neuroinflammation and depression: Microglia activation, extracellular microvesicles and microRNA dysregulation. Front. Cell. Neurosci. 2015 9 476 10.3389/fncel.2015.00476 26733805
    [Google Scholar]
  82. Prada I. Gabrielli M. Turola E. Iorio A. D’Arrigo G. Parolisi R. De Luca M. Pacifici M. Bastoni M. Lombardi M. Legname G. Cojoc D. Buffo A. Furlan R. Peruzzi F. Verderio C. Glia-to-neuron transfer of miRNAs via extracellular vesicles: A new mechanism underlying inflammation-induced synaptic alterations. Acta Neuropathol. 2018 135 4 529 550 10.1007/s00401‑017‑1803‑x 29302779
    [Google Scholar]
  83. Rajabi S. Sadegi K. Hajisobhani S. Kaveh M. Taghizadeh E. miR-146a and miR-155 as promising biomarkers for prognosis and diagnosis of multiple sclerosis: Systematic review. Egypt. J. Med. Hum. Genet. 2024 25 1 73 10.1186/s43042‑024‑00543‑0
    [Google Scholar]
  84. Mao S. Wu J. Yan J. Zhang W. Zhu F. Dysregulation of miR-146a: A causative factor in epilepsy pathogenesis, diagnosis, and prognosis. Front. Neurol. 2023 14 1094709 10.3389/fneur.2023.1094709 37213914
    [Google Scholar]
  85. Miller A.H. Raison C.L. The role of inflammation in depression: From evolutionary imperative to modern treatment target. Nat. Rev. Immunol. 2016 16 1 22 34 10.1038/nri.2015.5 26711676
    [Google Scholar]
  86. Borsini A. Zunszain P.A. Thuret S. Pariante C.M. The role of inflammatory cytokines as key modulators of neurogenesis. Trends Neurosci. 2015 38 3 145 157 10.1016/j.tins.2014.12.006 25579391
    [Google Scholar]
  87. Valiuliene G. Valiulis V. Zentelyte A. Dapsys K. Germanavicius A. Navakauskiene R. Anti-neuroinflammatory microRNA-146a-5p as a potential biomarker for neuronavigation-guided rTMS therapy success in medication resistant depression disorder. Biomed. Pharmacother. 2023 166 115313 10.1016/j.biopha.2023.115313 37572636
    [Google Scholar]
  88. Aslani M. Mortazavi-Jahromi S.S. Mirshafiey A. Efficient roles of miR-146a in cellular and molecular mechanisms of neuroinflammatory disorders: An effectual review in neuroimmunology. Immunol. Lett. 2021 238 1 20 10.1016/j.imlet.2021.07.004 34293378
    [Google Scholar]
  89. Lukiw W.J. microRNA-146a signaling in Alzheimer’s Disease (AD) and Prion Disease (PrD). Front. Neurol. 2020 11 462 10.3389/fneur.2020.00462 32670176
    [Google Scholar]
  90. Sabbatinelli J. Giuliani A. Matacchione G. Latini S. Laprovitera N. Pomponio G. Ferrarini A. Svegliati Baroni S. Pavani M. Moretti M. Gabrielli A. Procopio A.D. Ferracin M. Bonafè M. Olivieri F. Decreased serum levels of the inflammaging marker miR-146a are associated with clinical non-response to tocilizumab in COVID-19 patients. Mech. Ageing Dev. 2021 193 111413 10.1016/j.mad.2020.111413 33307107
    [Google Scholar]
  91. Han R. Gao J. Wang L. Hao P. Chen X. Wang Y. Jiang Z. Jiang L. Wang T. Zhu L. Li X. MicroRNA-146a negatively regulates inflammation via the IRAK1/TRAF6/NF-κB signaling pathway in dry eye. Sci. Rep. 2023 13 1 11192 10.1038/s41598‑023‑38367‑4 37433841
    [Google Scholar]
  92. Gong H. Chen H. Xiao P. Huang N. Han X. Zhang J. Yang Y. Li T. Zhao T. Tai H. Xu W. Zhang G. Gong C. Yang M. Tang X. Xiao H. miR-146a impedes the anti-aging effect of AMPK via NAMPT suppression and NAD+/SIRT inactivation. Signal Transduct. Target. Ther. 2022 7 1 66 10.1038/s41392‑022‑00886‑3 35241643
    [Google Scholar]
  93. Bhol N.K. Bhanjadeo M.M. Singh A.K. Dash U.C. Ojha R.R. Majhi S. Duttaroy A.K. Jena A.B. The interplay between cytokines, inflammation, and antioxidants: mechanistic insights and therapeutic potentials of various antioxidants and anti-cytokine compounds. Biomed. Pharmacother. 2024 178 117177 10.1016/j.biopha.2024.117177 39053423
    [Google Scholar]
  94. Chovatiya R. Medzhitov R. Stress, inflammation, and defense of homeostasis. Mol. Cell 2014 54 2 281 288 10.1016/j.molcel.2014.03.030 24766892
    [Google Scholar]
  95. Reist C. Petiwala I. Latimer J. Raffaelli S.B. Chiang M. Eisenberg D. Campbell S. Collaborative mental health care: A narrative review. Medicine (Baltimore) 2022 101 52 e32554 10.1097/MD.0000000000032554 36595989
    [Google Scholar]
  96. Hou Q. Ruan H. Gilbert J. Wang G. Ma Q. Yao W.D. Man H.Y. MicroRNA miR124 is required for the expression of homeostatic synaptic plasticity. Nat. Commun. 2015 6 1 10045 10.1038/ncomms10045 26620774
    [Google Scholar]
  97. Wohl S.G. Hooper M.J. Reh T.A. MicroRNAs miR-25, let-7 and miR-124 regulate the neurogenic potential of Müller glia in mice. Development 2019 146 17 dev.179556 10.1242/dev.179556 31383796
    [Google Scholar]
  98. Son G. Na Y. Kim Y. Son J.H. Clemenson G.D. Schafer S.T. Yoo J.Y. Parylak S.L. Paquola A. Do H. Kim D. Ahn I. Ju M. Kang C.S. Ju Y. Jung E. McDonald A.H. Park Y. Kim G. Paik S.B. Hur J. Kim J. Han Y.M. Lee S.H. Gage F.H. Kim J.S. Han J. miR-124 coordinates metabolic regulators acting at early stages of human neurogenesis. Commun. Biol. 2024 7 1 1393 10.1038/s42003‑024‑07089‑2 39455851
    [Google Scholar]
  99. Liang C. Zou T. Zhang M. Fan W. Zhang T. Jiang Y. Cai Y. Chen F. Chen X. Sun Y. Zhao B. Wang Y. Cui L. MicroRNA-146a switches microglial phenotypes to resist the pathological processes and cognitive degradation of Alzheimer’s disease. Theranostics 2021 11 9 4103 4121 10.7150/thno.53418 33754051
    [Google Scholar]
  100. Rohleder N. Kirschbaum C. The hypothalamic–pituitary–adrenal (HPA) axis in habitual smokers. Int. J. Psychophysiol. 2006 59 3 236 243 10.1016/j.ijpsycho.2005.10.012 16325948
    [Google Scholar]
  101. Leistner C. Menke A. Hypothalamic–pituitary–adrenal axis and stress. Handb. Clin. Neurol. 2020 175 55 64 10.1016/B978‑0‑444‑64123‑6.00004‑7 33008543
    [Google Scholar]
  102. DeMorrow S. Role of the hypothalamic–pituitary–adrenal axis in health and disease. Int. J. Mol. Sci. 2018 19 986 10.3390/ijms19040986
    [Google Scholar]
  103. Kim T. Croce C.M. MicroRNA: trends in clinical trials of cancer diagnosis and therapy strategies. Exp. Mol. Med. 2023 55 7 1314 1321 10.1038/s12276‑023‑01050‑9 37430087
    [Google Scholar]
  104. Shaheen N. Shaheen A. Osama M. Nashwan A.J. Bharmauria V. Flouty O. MicroRNAs regulation in Parkinson’s disease, and their potential role as diagnostic and therapeutic targets. NPJ Parkinsons Dis. 2024 10 1 186 10.1038/s41531‑024‑00791‑2 39369002
    [Google Scholar]
  105. Artimovič P. Špaková I. Macejková E. Pribulová T. Rabajdová M. Mareková M. Zavacká M. The ability of microRNAs to regulate the immune response in ischemia/reperfusion inflammatory pathways. Genes Immun. 2024 25 4 277 296 10.1038/s41435‑024‑00283‑6 38909168
    [Google Scholar]
  106. Bhatnagar D. Ladhe S. Kumar D. Discerning the prospects of miRNAs as a multi-target therapeutic and diagnostic for alzheimer’s disease. Mol. Neurobiol. 2023 60 10 5954 5974 10.1007/s12035‑023‑03446‑0 37386272
    [Google Scholar]
  107. Sørensen S.S. Nygaard A.B. Christensen T. miRNA expression profiles in cerebrospinal fluid and blood of patients with Alzheimer’s disease and other types of dementia: An exploratory study. Transl. Neurodegener. 2016 5 1 6 10.1186/s40035‑016‑0053‑5 26981236
    [Google Scholar]
  108. Pritchard C.C. Cheng H.H. Tewari M. MicroRNA profiling: Approaches and considerations. Nat. Rev. Genet. 2012 13 5 358 369 10.1038/nrg3198 22510765
    [Google Scholar]
  109. Herzog C.M.S. Goeminne L.J.E. Poganik J.R. Barzilai N. Belsky D.W. Betts-LaCroix J. Chen B.H. Chen M. Cohen A.A. Cummings S.R. Fedichev P.O. Ferrucci L. Fleming A. Fortney K. Furman D. Gorbunova V. Higgins-Chen A. Hood L. Horvath S. Justice J.N. Kiel D.P. Kuchel G.A. Lasky-Su J. LeBrasseur N.K. Maier A.B. Schilling B. Sebastiano V. Slagboom P.E. Snyder M.P. Verdin E. Widschwendter M. Zhavoronkov A. Moqri M. Gladyshev V.N. Biomarkers of Aging Consortium Challenges and recommendations for the translation of biomarkers of aging. Nat. Aging 2024 4 10 1372 1383 10.1038/s43587‑024‑00683‑3 39285015
    [Google Scholar]
  110. Karlsson L. Vogel J. Arvidsson I. Åström K. Janelidze S. Blennow K. Palmqvist S. Stomrud E. Mattsson-Carlgren N. Hansson O. Cerebrospinal fluid reference proteins increase accuracy and interpretability of biomarkers for brain diseases. Nat. Commun. 2024 15 1 3676 10.1038/s41467‑024‑47971‑5 38693142
    [Google Scholar]
  111. Mancuso E. Sampogna G. Boiano A. Della Rocca B. Di Vincenzo M. Lapadula M.V. Martinelli F. Lucci F. Luciano M. Biological correlates of treatment resistant depression: A review of peripheral biomarkers. Front. Psychiatry 2023 14 1291176 10.3389/fpsyt.2023.1291176 37941970
    [Google Scholar]
  112. Das S. Dey M.K. Devireddy R. Gartia M.R. Biomarkers in cancer detection, diagnosis, and prognosis. Sensors 2023 24 1 37 10.3390/s24010037 38202898
    [Google Scholar]
  113. Rydzewski N.R. Peterson E. Lang J.M. Yu M. Laura Chang S. Sjöström M. Bakhtiar H. Song G. Helzer K.T. Bootsma M.L. Chen W.S. Shrestha R.M. Zhang M. Quigley D.A. Aggarwal R. Small E.J. Wahl D.R. Feng F.Y. Zhao S.G. Predicting cancer drug TARGETS - TreAtment response generalized elastic-neT signatures. NPJ Genom. Med. 2021 6 1 76 10.1038/s41525‑021‑00239‑z 34548481
    [Google Scholar]
  114. Lopez J.P. Lim R. Cruceanu C. Crapper L. Fasano C. Labonte B. Maussion G. Yang J.P. Yerko V. Vigneault E. El Mestikawy S. Mechawar N. Pavlidis P. Turecki G. miR-1202 is a primate-specific and brain-enriched microRNA involved in major depression and antidepressant treatment. Nat. Med. 2014 20 7 764 768 10.1038/nm.3582 24908571
    [Google Scholar]
  115. Shang C. Chen Q. Zu F. Ren W. Integrated analysis identified prognostic microRNAs in breast cancer. BMC Cancer 2022 22 1 1170 10.1186/s12885‑022‑10242‑x 36371182
    [Google Scholar]
  116. Wang X. Wang B. Zhao J. Liu C. Qu X. Li Y. MiR-155 is involved in major depression disorder and antidepressant treatment via targeting SIRT1. Biosci. Rep. 2018 38 6 BSR20181139 10.1042/BSR20181139 30482883
    [Google Scholar]
  117. Chua C.E.L. Tang B.L. miR-34a in neurophysiology and neuropathology. J. Mol. Neurosci. 2019 67 2 235 246 10.1007/s12031‑018‑1231‑y 30488149
    [Google Scholar]
  118. Muñoz-San Martín M. Reverter G. Robles-Cedeño R. Buxò M. Ortega F.J. Gómez I. Tomàs-Roig J. Celarain N. Villar L.M. Perkal H. Fernández-Real J.M. Quintana E. Ramió-Torrentà L. Analysis of miRNA signatures in CSF identifies upregulation of miR-21 and miR-146a/b in patients with multiple sclerosis and active lesions. J. Neuroinflammation 2019 16 1 220 10.1186/s12974‑019‑1590‑5 31727077
    [Google Scholar]
  119. Zhang C. Sun C. Zhao Y. Wang Q. Guo J. Ye B. Yu G. Overview of MicroRNAs as diagnostic and prognostic biomarkers for high-incidence cancers in 2021. Int. J. Mol. Sci. 2022 23 19 11389 10.3390/ijms231911389 36232692
    [Google Scholar]
  120. Demyttenaere K. Van Duppen Z. The impact of (the Concept of) treatment-resistant depression: An opinion review. Int. J. Neuropsychopharmacol. 2019 22 2 85 92 10.1093/ijnp/pyy052 29961822
    [Google Scholar]
  121. Borbély É. Simon M. Fuchs E. Wiborg O. Czéh B. Helyes Z. Novel drug developmental strategies for treatment‐resistant depression. Br. J. Pharmacol. 2022 179 6 1146 1186 10.1111/bph.15753 34822719
    [Google Scholar]
  122. Lopez J.P. Fiori L.M. Cruceanu C. Lin R. Labonte B. Cates H.M. Heller E.A. Vialou V. Ku S.M. Gerald C. Han M.H. Foster J. Frey B.N. Soares C.N. Müller D.J. Farzan F. Leri F. MacQueen G.M. Feilotter H. Tyryshkin K. Evans K.R. Giacobbe P. Blier P. Lam R.W. Milev R. Parikh S.V. Rotzinger S. Strother S.C. Lewis C.M. Aitchison K.J. Wittenberg G.M. Mechawar N. Nestler E.J. Uher R. Kennedy S.H. Turecki G. MicroRNAs 146a/b-5 and 425-3p and 24-3p are markers of antidepressant response and regulate MAPK/Wnt-system genes. Nat. Commun. 2017 8 1 15497 10.1038/ncomms15497 28530238
    [Google Scholar]
  123. Vidigal J.A. Ventura A. The biological functions of miRNAs: Lessons from in vivo studies. Trends Cell Biol. 2015 25 3 137 147 10.1016/j.tcb.2014.11.004 25484347
    [Google Scholar]
  124. Sandau U.S. Wiedrick J.T. McFarland T.J. Galasko D.R. Fanning Z. Quinn J.F. Saugstad J.A. Analysis of the longitudinal stability of human plasma miRNAs and implications for disease biomarkers. Sci. Rep. 2024 14 1 2148 10.1038/s41598‑024‑52681‑5 38272952
    [Google Scholar]
  125. Ma S. Yu J. Qin X. Liu J. Current status and challenges in establishing reference intervals based on real-world data. Crit. Rev. Clin. Lab. Sci. 2023 60 6 427 441 10.1080/10408363.2023.2195496 37038925
    [Google Scholar]
  126. Rush A.J. Trivedi M.H. Wisniewski S.R. Nierenberg A.A. Stewart J.W. Warden D. Niederehe G. Thase M.E. Lavori P.W. Lebowitz B.D. McGrath P.J. Rosenbaum J.F. Sackeim H.A. Kupfer D.J. Luther J. Fava M. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: A STAR*D report. Am. J. Psychiatry 2006 163 11 1905 1917 10.1176/ajp.2006.163.11.1905 17074942
    [Google Scholar]
  127. Gururajan A. Naughton M.E. Scott K.A. O’Connor R.M. Moloney G. Clarke G. Dowling J. Walsh A. Ismail F. Shorten G. Scott L. McLoughlin D.M. Cryan J.F. Dinan T.G. MicroRNAs as biomarkers for major depression: A role for let-7b and let-7c. Transl. Psychiatry 2016 6 8 e862 e862 10.1038/tp.2016.131 27483380
    [Google Scholar]
  128. Dwivedi Y. MicroRNAs in depression and suicide: Recent insights and future perspectives. J. Affect. Disord. 2018 240 146 154 10.1016/j.jad.2018.07.075 30071418
    [Google Scholar]
  129. Shi Y. Wang Q. Song R. Kong Y. Zhang Z. Non-coding RNAs in depression: Promising diagnostic and therapeutic biomarkers. EBioMedicine 2021 71 103569 10.1016/j.ebiom.2021.103569 34521053
    [Google Scholar]
  130. Fang Y. Qiu Q. Zhang S. Sun L. Li G. Xiao S. Li X. Changes in miRNA-132 and miR-124 levels in non-treated and citalopram-treated patients with depression. J. Affect. Disord. 2018 227 745 751 10.1016/j.jad.2017.11.090 29689690
    [Google Scholar]
  131. Żurawek D. Turecki G. The miRNome of depression. Int. J. Mol. Sci. 2021 22 21 11312 10.3390/ijms222111312 34768740
    [Google Scholar]
  132. Maffioletti E. Bocchio-Chiavetto L. Perusi G. Carvalho Silva R. Sacco C. Bazzanella R. Zampieri E. Bortolomasi M. Gennarelli M. Minelli A. Inflammation-related microRNAs are involved in stressful life events exposure and in trauma-focused psychotherapy in treatment-resistant depressed patients. Eur. J. Psychotraumatol. 2021 12 1 1987655 10.1080/20008198.2021.1987655 35070159
    [Google Scholar]
  133. Alural B. Genc S. Haggarty S.J. Diagnostic and therapeutic potential of microRNAs in neuropsychiatric disorders: Past, present, and future. Prog. Neuropsychopharmacol. Biol. Psychiatry 2017 73 87 103 10.1016/j.pnpbp.2016.03.010 27072377
    [Google Scholar]
  134. Sørensen S.S. Nygaard A.B. Nielsen M.Y. Jensen K. Christensen T. miRNA expression profiles in cerebrospinal fluid and blood of patients with acute ischemic stroke. Transl. Stroke Res. 2014 5 6 711 718 10.1007/s12975‑014‑0364‑8 25127724
    [Google Scholar]
  135. Atif H. Hicks S.D. A review of MicroRNA biomarkers in traumatic brain injury. J. Exp. Neurosci. 2019 13 1179069519832286 10.1177/1179069519832286 30886525
    [Google Scholar]
  136. Dave V.P. Ngo T.A. Pernestig A.K. Tilevik D. Kant K. Nguyen T. Wolff A. Bang D.D. MicroRNA amplification and detection technologies: Opportunities and challenges for point of care diagnostics. Lab. Invest. 2019 99 4 452 469 10.1038/s41374‑018‑0143‑3 30542067
    [Google Scholar]
  137. Liu G. Ladrón-de-Guevara A. Izhiman Y. Nedergaard M. Du T. Measurements of cerebrospinal fluid production: A review of the limitations and advantages of current methodologies. Fluids Barriers CNS 2022 19 1 101 10.1186/s12987‑022‑00382‑4 36522656
    [Google Scholar]
  138. Li Y.B. Fu Q. Guo M. Du Y. Chen Y. Cheng Y. MicroRNAs: Pioneering regulators in Alzheimer’s disease pathogenesis, diagnosis, and therapy. Transl. Psychiatry 2024 14 1 367 10.1038/s41398‑024‑03075‑8 39256358
    [Google Scholar]
  139. Ma Y.M. Zhao L. Mechanism and therapeutic prospect of miRNAs in neurodegenerative diseases. Behav. Neurol. 2023 2023 1 24 10.1155/2023/8537296 38058356
    [Google Scholar]
  140. Jiang X. Xiang G. Wang Y. Zhang L. Yang X. Cao L. Peng H. Xue P. Chen D. MicroRNA-590-5p regulates proliferation and invasion in human hepatocellular carcinoma cells by targeting TGF-β RII. Mol. Cells 2012 33 6 545 552 10.1007/s10059‑012‑2267‑4 22684895
    [Google Scholar]
  141. Barwal T.S. Singh N. Sharma U. Bazala S. Rani M. Behera A. Kumawat R.K. Kumar P. Uttam V. Khandelwal A. Barwal J. Jain M. Jain A. miR-590–5p: A double-edged sword in the oncogenesis process. Cancer Treat. Res. Commun. 2022 32 100593 10.1016/j.ctarc.2022.100593 35752082
    [Google Scholar]
  142. Deng Z. Fan T. Xiao C. Tian H. Zheng Y. Li C. He J. TGF-β signaling in health, disease and therapeutics. Signal Transduct. Target. Ther. 2024 9 1 61 10.1038/s41392‑024‑01764‑w 38514615
    [Google Scholar]
  143. Metcalf G.A.D. MicroRNAs: circulating biomarkers for the early detection of imperceptible cancers via biosensor and machine-learning advances. Oncogene 2024 43 28 2135 2142 10.1038/s41388‑024‑03076‑3 38839942
    [Google Scholar]
  144. Yoon H. Belmonte K.C. Kasten T. Bateman R. Kim J. Intra- and Inter-individual variability of microRNA levels in human cerebrospinal fluid: Critical implications for biomarker discovery. Sci. Rep. 2017 7 1 12720 10.1038/s41598‑017‑13031‑w 28983117
    [Google Scholar]
  145. Zhang W.H. Jiang L. Li M. Liu J. MicroRNA‑124: an emerging therapeutic target in central nervous system disorders. Exp. Brain Res. 2023 241 5 1215 1226 10.1007/s00221‑022‑06524‑2 36961552
    [Google Scholar]
  146. Li N. Pan X. Zhang J. Ma A. Yang S. Ma J. Xie A. Plasma levels of miR-137 and miR-124 are associated with Parkinson’s disease but not with Parkinson’s disease with depression. Neurol. Sci. 2017 38 5 761 767 10.1007/s10072‑017‑2841‑9 28181066
    [Google Scholar]
  147. Angelopoulou E. Paudel Y.N. Piperi C. miR-124 and Parkinson’s disease: A biomarker with therapeutic potential. Pharmacol. Res. 2019 150 104515 10.1016/j.phrs.2019.104515 31707035
    [Google Scholar]
  148. Lai G. Malavolta M. Marcozzi S. Bigossi G. Giuliani M.E. Casoli T. Balietti M. Late-onset major depressive disorder: Exploring the therapeutic potential of enhancing cerebral brain-derived neurotrophic factor expression through targeted microRNA delivery. Transl. Psychiatry 2024 14 1 352 10.1038/s41398‑024‑02935‑7 39227372
    [Google Scholar]
  149. Rupaimoole R. Slack F.J. MicroRNA therapeutics: Towards a new era for the management of cancer and other diseases. Nat. Rev. Drug Discov. 2017 16 3 203 222 10.1038/nrd.2016.246 28209991
    [Google Scholar]
  150. Brennan G.P. Henshall D.C. MicroRNAs as regulators of brain function and targets for treatment of epilepsy. Nat. Rev. Neurol. 2020 16 9 506 519 10.1038/s41582‑020‑0369‑8 32546757
    [Google Scholar]
  151. Rose S.A. Wroblewska A. Dhainaut M. Yoshida H. Shaffer J.M. Bektesevic A. Ben-Zvi B. Rhoads A. Kim E.Y. Yu B. Lavin Y. Merad M. Buenrostro J.D. Brown B.D. Aguilar O. Allan R. Arakawa-Hoyt J. Astarita J. Austen K.F. Barrett N. Baysoy A. Benoist C. Buechler M. Buenrostro J. Casanova M.A. Choi K. Chowdhary K. Colonna M. Crowl T. Deng T. Desai J.V. Desland F. Ding J. Dominguez C. Dwyer D. Frascoli M. Gal-Oz S. Goldrath A. Grieshaber-Bouyer R. Jia B. Johanson T. Jordan S. Kang J. Kapoor V. Kenigsberg E. Kim J. Kim K. Kiner E. Kronenberg M. Lanier L. Laplace C. Lareau C. Leader A. Lee J. Magen A. Maier B. Maslova A. Mathis D. McFarland A. Meunier E. Monach P. Mostafavi S. Muller S. Muus C. Ner-Gaon H. Nguyen Q. Nigrovic P.A. Niizuma K. Novakovsky G. Nutt S. Omilusik K. Ortiz-Lopez A. Paynich M. Peng V. Potempa M. Pradhan R. Quon S. Ramirez R. Ramanan D. Randolph G. Regev A. Seddu K. Shay T. Shemesh A. Shyer J. Smilie C. Spidale N. Subramanian A. Sylvia K. Tellier J. Turley S. Vijaykumar B. Wagers A. Wang C. Wang P.L. Yang L. Yim A. Immunological Genome Consortium A microRNA expression and regulatory nlm activity atlas of the mouse immune system. Nat. Immunol. 2021 22 7 914 927 10.1038/s41590‑021‑00944‑y 34099919
    [Google Scholar]
  152. Papadimitriou E. Koutsoudaki P.N. Thanou I. Karagkouni D. Karamitros T. Chroni-Tzartou D. Gaitanou M. Gkemisis C. Margariti M. Xingi E. Tzartos S.J. Hatzigeorgiou A.G. Thomaidou D. A miR-124-mediated post-transcriptional mechanism controlling the cell fate switch of astrocytes to induced neurons. Stem Cell Reports 2023 18 4 915 935 10.1016/j.stemcr.2023.02.009 36963393
    [Google Scholar]
  153. Krützfeldt J. Rajewsky N. Braich R. Rajeev K.G. Tuschl T. Manoharan M. Stoffel M. Silencing of microRNAs in vivo with ‘antagomirs’. Nature 2005 438 7068 685 689 10.1038/nature04303 16258535
    [Google Scholar]
  154. Kaurani L. Clinical insights into MicroRNAs in depression: Bridging molecular discoveries and therapeutic potential. Int. J. Mol. Sci. 2024 25 5 2866 10.3390/ijms25052866 38474112
    [Google Scholar]
  155. Xu Y.Y. Xia Q. Xia Q. Zhang X. Liang J. MicroRNA-based biomarkers in the diagnosis and monitoring of therapeutic response in patients with depression. Neuropsychiatr. Dis. Treat. 2019 15 3583 3597 10.2147/NDT.S237116 31920318
    [Google Scholar]
  156. Frodl T. Recent advances in predicting responses to antidepressant treatment. F1000 Res. 2017 6 619 10.12688/f1000research.10300.1 28529691
    [Google Scholar]
  157. Fiori L.M. Orri M. Aouabed Z. Théroux J.F. Lin R. Nagy C. Frey B.N. Lam R.W. MacQueen G.M. Milev R. Müller D.J. Parikh S.V. Rotzinger S. Uher R. Foster J.A. Kennedy S.H. Turecki G. Treatment-emergent and trajectory-based peripheral gene expression markers of antidepressant response. Transl. Psychiatry 2021 11 1 439 10.1038/s41398‑021‑01564‑8 34420030
    [Google Scholar]
  158. Wu D. Chen Q. Chen X. Han F. Chen Z. Wang Y. The blood–brain barrier: Structure, regulation and drug delivery. Signal Transduct. Target. Ther. 2023 8 1 217 10.1038/s41392‑023‑01481‑w 37231000
    [Google Scholar]
  159. Gao J. Gunasekar S. Xia Z. Shalin K. Jiang C. Chen H. Lee D. Lee S. Pisal N.D. Luo J.N. Griciuc A. Karp J.M. Tanzi R. Joshi N. Gene therapy for CNS disorders: Modalities, delivery and translational challenges. Nat. Rev. Neurosci. 2024 25 8 553 572 10.1038/s41583‑024‑00829‑7 38898231
    [Google Scholar]
  160. O’Brien J. Hayder H. Zayed Y. Peng C. Overview of MicroRNA biogenesis, mechanisms of actions, and circulation. Front. Endocrinol. (Lausanne) 2018 9 402 10.3389/fendo.2018.00402 30123182
    [Google Scholar]
  161. Momin M.Y. Gaddam R.R. Kravitz M. Gupta A. Vikram A. The challenges and opportunities in the development of microrna therapeutics: a multidisciplinary viewpoint. Cells 2021 10 11 3097 10.3390/cells10113097 34831320
    [Google Scholar]
  162. Munsie M. Gyngell C. Ethical issues in genetic modification and why application matters. Curr. Opin. Genet. Dev. 2018 52 7 12 10.1016/j.gde.2018.05.002 29800628
    [Google Scholar]
  163. Farmer L. Lundy A. Informed consent: Ethical and legal considerations for advanced practice nurses. J. Nurse Pract. 2017 13 2 124 130 10.1016/j.nurpra.2016.08.011
    [Google Scholar]
  164. Gawne P.J. Ferreira M. Papaluca M. Grimm J. Decuzzi P. New opportunities and old challenges in the clinical translation of nanotheranostics. Nat. Rev. Mater. 2023 8 12 783 798 10.1038/s41578‑023‑00581‑x 39022623
    [Google Scholar]
  165. Yu Z. Coorens T.H.H. Uddin M.M. Ardlie K.G. Lennon N. Natarajan P. Genetic variation across and within individuals. Nat. Rev. Genet. 2024 25 8 548 562 10.1038/s41576‑024‑00709‑x 38548833
    [Google Scholar]
  166. Olive P. Hives L. Wilson N. Ashton A. O’Brien M.C. Mercer G. Jassat R. Harris C. Psychological and psychosocial aspects of major trauma care in the United Kingdom: A scoping review of primary research. Trauma 2023 25 4 338 347 10.1177/14604086221104934
    [Google Scholar]
  167. Ghebrehiwet I. Zaki N. Damseh R. Mohamad M.S. Revolutionizing personalized medicine with generative AI: A systematic review. Artif. Intell. Rev. 2024 57 5 128 10.1007/s10462‑024‑10768‑5
    [Google Scholar]
  168. Malhi G.S. Mann J.J. Depression. Lancet 2018 392 10161 2299 2312 10.1016/S0140‑6736(18)31948‑2 30396512
    [Google Scholar]
  169. Singh A. Kar S.K. How electroconvulsive therapy works?: Understanding the neurobiological mechanisms. Clin. Psychopharmacol. Neurosci. 2017 15 3 210 221 10.9758/cpn.2017.15.3.210 28783929
    [Google Scholar]
  170. Ousdal O.T. Brancati G.E. Kessler U. Erchinger V. Dale A.M. Abbott C. Oltedal L. The neurobiological effects of electroconvulsive therapy studied through magnetic resonance: hat have we learned, and where do we go? Biol. Psychiatry 2022 91 6 540 549 10.1016/j.biopsych.2021.05.023 34274106
    [Google Scholar]
  171. Sandhanam K. Tamilanban T. Bhattacharjee B. Manasa K. Exploring miRNA therapies and gut microbiome–enhanced CAR-T cells: Advancing frontiers in glioblastoma stem cell targeting. Naunyn Schmiedebergs Arch. Pharmacol. 2024 2024 10.1007/s00210‑024‑03479‑9 39382681
    [Google Scholar]
  172. Prabhakaran R. Thamarai R. Sivasamy S. Dhandayuthapani S. Batra J. Kamaraj C. Karthik K. Shah M.A. Mallik S. Epigenetic frontiers: MiRNAs, long non-coding RNAs and nanomaterials are pioneering to cancer therapy. Epigenetics Chromatin 2024 17 1 31 10.1186/s13072‑024‑00554‑6 39415281
    [Google Scholar]
  173. Zheng K. Hu F. Zhou Y. Zhang J. Zheng J. Lai C. Xiong W. Cui K. Hu Y.Z. Han Z.T. Zhang H.H. Chen J.G. Man H.Y. Liu D. Lu Y. Zhu L.Q. miR-135a-5p mediates memory and synaptic impairments via the Rock2/Adducin1 signaling pathway in a mouse model of Alzheimer’s disease. Nat. Commun. 2021 12 1 1903 10.1038/s41467‑021‑22196‑y 33771994
    [Google Scholar]
  174. Zhang S. Cheng Z. Wang Y. Han T. The Risks of miRNA therapeutics: In a drug target perspective. Drug Des. Devel. Ther. 2021 15 721 733 10.2147/DDDT.S288859 33654378
    [Google Scholar]
  175. Frasco M.F. Almeida G.M. Santos-Silva F. Pereira M.C. Coelho M.A.N. Transferrin surface-modified PLGA nanoparticles-mediated delivery of a proteasome inhibitor to human pancreatic cancer cells. J. Biomed. Mater. Res. A 2015 103 4 1476 1484 10.1002/jbm.a.35286 25046528
    [Google Scholar]
  176. Ghafouri-Fard S. Shoorei H. Noferesti L. Hussen B.M. Moghadam M.H.B. Taheri M. Rashnoo F. Nanoparticle-mediated delivery of microRNAs-based therapies for treatment of disorders. Pathol. Res. Pract. 2023 248 154667 10.1016/j.prp.2023.154667 37422972
    [Google Scholar]
  177. Rizg W.Y. Alghamdi M.A. Saadany S.E. Madkhali O.A. Nair A.K. Rashid M.A. Kotta S. Recent advances and future prospects of engineered exosomes as advanced drug and gene delivery systems. J. Drug Deliv. Sci. Technol. 2025 106 106696 10.1016/j.jddst.2025.106696
    [Google Scholar]
/content/journals/crcep/10.2174/0127724328381443250825092900
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MicroRNAs as Biomarkers and Therapeutic Targets in Treatment-Resistant Depression: Unveiling Diagnostic and Treatment Pathways
Bentham Science Publishers ; https://doi.org/10.2174/0127724328381443250825092900
/content/journals/crcep/10.2174/0127724328381443250825092900
/content/journals/crcep/10.2174/0127724328381443250825092900
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  • Article Type:     Review Article
Keywords: MicroRNAs (miRNAs) ; Treatment-resistant depression (TRD) ; precision psychiatry ; neuroinflammation ; biomarkers ; miRNA-based therapeutics ; antidepressant resistance

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