{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T12:08:29Z","timestamp":1781006909805,"version":"3.54.1"},"reference-count":79,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2020,7,18]],"date-time":"2020-07-18T00:00:00Z","timestamp":1595030400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["EY006311"],"award-info":[{"award-number":["EY006311"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["AG18031"],"award-info":[{"award-number":["AG18031"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["AG038834"],"award-info":[{"award-number":["AG038834"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Exosomes (EXs) and extracellular microvesicles (EMVs) represent a diverse assortment of plasma membrane-derived nanovesicles, 30\u20131000 nm in diameter, released by all cell lineages of the central nervous system (CNS). They are examples of a very active and dynamic form of extracellular communication and the conveyance of biological information transfer essential to maintain homeostatic neurological functions and contain complex molecular cargoes representative of the cytoplasm of their cells of origin. These molecular cargoes include various mixtures of proteins, lipids, proteolipids, cytokines, chemokines, carbohydrates, microRNAs (miRNA) and messenger RNAs (mRNA) and other components, including end-stage neurotoxic and pathogenic metabolic products, such as amyloid beta (A\u03b2) peptides. Brain microglia, for example, respond to both acute CNS injuries and degenerative diseases with complex reactions via the induction of a pro-inflammatory phenotype, and secrete EXs and EMVs enriched in selective pathogenic microRNAs (miRNAs) such as miRNA-34a, miRNA-125b, miRNA-146a, miRNA-155, and others that are known to promote neuro-inflammation, induce complement activation, disrupt innate\u2013immune signaling and deregulate the expression of neuron-specific phosphoproteins involved in neurotropism and synaptic signaling. This communication will review our current understanding of the trafficking of miRNA-containing EXs and EMVs from astrocytes and \u201cactivated pro-inflammatory\u201d microglia to target neurons in neurodegenerative diseases with an emphasis on Alzheimer\u2019s disease wherever possible.<\/jats:p>","DOI":"10.3390\/ijms21145078","type":"journal-article","created":{"date-parts":[[2020,7,20]],"date-time":"2020-07-20T06:08:17Z","timestamp":1595225297000},"page":"5078","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Vesicular Transport of Encapsulated microRNA between Glial and Neuronal Cells"],"prefix":"10.3390","volume":"21","author":[{"given":"Walter J.","family":"Lukiw","sequence":"first","affiliation":[{"name":"Departments of Neurology, Neuroscience and Ophthalmology, Neuroscience Center and Department of Ophthalmology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA"},{"name":"LSU Neuroscience Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA"},{"name":"Department of Ophthalmology, LSU Health Sciences Center, New Orleans, LA 70112, USA"},{"name":"Department of Neurology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aileen I.","family":"Pogue","sequence":"additional","affiliation":[{"name":"Alchem Biotech Research, Toronto, ON M5S1A8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1146\/annurev-cellbio-101512-122326","article-title":"Biogenesis, Secretion, and Intercellular Interactions of Exosomes and Other Extracellular Vesicles","volume":"30","author":"Colombo","year":"2014","journal-title":"Annu. Rev. Cell Dev. Boil."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1002\/mas.21420","article-title":"Proteomics of extracellular vesicles: Exosomes and ectosomes","volume":"34","author":"Choi","year":"2014","journal-title":"Mass Spectrom. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"6156","DOI":"10.1007\/s12035-019-1500-y","article-title":"Systematic Review of miRNA as Biomarkers in Alzheimer\u2019s Disease","volume":"56","author":"Swarbrick","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3392","DOI":"10.4049\/jimmunol.1801008","article-title":"Circulating Plasma Extracellular Vesicles from Septic Mice Induce Inflammation via MicroRNA- and TLR7-Dependent Mechanisms","volume":"201","author":"Xu","year":"2018","journal-title":"J. Immunol."},{"key":"ref_5","first-page":"11","article-title":"Exosomes and microvesicles in normal physiology, pathophysiology, and renal diseases","volume":"34","author":"Johansson","year":"2017","journal-title":"Pediatr. Nephrol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"101006","DOI":"10.1016\/j.arr.2019.101006","article-title":"Endosomal dysfunction impacts extracellular vesicle release: Central role in A\u03b2 pathology","volume":"58","author":"Arbo","year":"2020","journal-title":"Ageing Res. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1007\/s10571-019-00751-y","article-title":"Specific Signatures of Serum miRNAs as Potential Biomarkers to Discriminate Clinically Similar Neurodegenerative and Vascular-Related Diseases","volume":"40","author":"Barbagallo","year":"2019","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"jcs228114","DOI":"10.1242\/jcs.228114","article-title":"Autophagy and endocytosis \u2013 interconnections and interdependencies","volume":"133","author":"Birgisdottir","year":"2020","journal-title":"J. Cell Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"79","DOI":"10.3389\/fnmol.2020.00079","article-title":"Brain Derived Exosomes Are a Double-Edged Sword in Alzheimer\u2019s Disease","volume":"13","author":"Song","year":"2020","journal-title":"Front. Mol. Neurosci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/nrm.2017.125","article-title":"Shedding light on the cell biology of extracellular vesicles","volume":"19","author":"Raposo","year":"2018","journal-title":"Nat. Rev. Mol. Cell Boil."},{"key":"ref_11","first-page":"129657","article-title":"Non-contact microfluidic mechanical property measurements of single apoptotic bodies","volume":"129657","author":"Dahl","year":"2020","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Gen. Subj."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Tabata, H. (2015). Diverse subtypes of astrocytes and their development during corticogenesis. Front. Mol. Neurosci., 9.","DOI":"10.3389\/fnins.2015.00114"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1007\/s12035-015-9105-6","article-title":"Analysis of RNA from Alzheimer\u2019s Disease Post-mortem Brain Tissues","volume":"53","author":"Clement","year":"2015","journal-title":"Mol. Neurobiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/s11010-020-03703-z","article-title":"Inside(sight) of tiny communicator: Exosome biogenesis, secretion, and uptake","volume":"467","author":"Jadli","year":"2020","journal-title":"Mol. Cell. Biochem."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Mathews, P., and Levy, E. (2019). Exosome Production Is Key to Neuronal Endosomal Pathway Integrity in Neurodegenerative Diseases. Front. Mol. Neurosci., 13.","DOI":"10.3389\/fnins.2019.01347"},{"key":"ref_16","unstructured":"Martins, T.S., Trindade, D., Vaz, M., Campelo, I., Almeida, M., Trigo, G., Silva, O.A., and Henriques, A.G. (2020). Diagnostic and therapeutic potential of exosomes in Alzheimer\u2019s disease [published online ahead of print. J. Neurochem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"153","DOI":"10.3389\/fgene.2019.00153","article-title":"MicroRNAs in Alzheimer\u2019s Disease","volume":"10","author":"Wang","year":"2019","journal-title":"Front. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Hunter, M.P., Ismail, N., Zhang, X., Aguda, B.D., Lee, E.J., Yu, L., Xiao, T., Schafer, J., Lee, M.-L.T., and Schmittgen, T.D. (2008). Detection of microRNA Expression in Human Peripheral Blood Microvesicles. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0003694"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.ymeth.2020.01.008","article-title":"Unraveling the mechanisms that specify molecules for secretion in extracellular vesicles","volume":"177","author":"Leidal","year":"2020","journal-title":"Methods"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.jconrel.2020.04.017","article-title":"Astrocyte-derived extracellular vesicles: Neuroreparative properties and role in the pathogenesis of neurodegenerative disorders","volume":"323","author":"Upadhya","year":"2020","journal-title":"J. Control Release"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1007\/s00401-017-1803-x","article-title":"Glia-to-neuron transfer of miRNAs via extracellular vesicles: A new mechanism underlying inflammation-induced synaptic alterations","volume":"135","author":"Prada","year":"2018","journal-title":"Acta Neuropathol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Serpente, M., Fenoglio, C., D\u2019Anca, M., Arcaro, M., Sorrentino, F., Visconte, C., Arighi, A., Fumagalli, G., Porretti, L., and Cattaneo, A. (2020). MiRNA Profiling in Plasma Neural-Derived Small Extracellular Vesicles from Patients with Alzheimer\u2019s Disease. Cells, 9.","DOI":"10.3390\/cells9061443"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1007\/s13238-015-0168-y","article-title":"Secreted miR-34a in astrocytic shedding vesicles enhanced the vulnerability of dopaminergic neurons to neurotoxins by targeting Bcl-2","volume":"6","author":"Mao","year":"2015","journal-title":"Protein Cell"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41556-018-0250-9","article-title":"Thery Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication","volume":"21","year":"2019","journal-title":"Nat. Cell Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1186\/s13287-020-01702-x","article-title":"Extracellular vesicles derived from human ES-MSCs protect retinal ganglion cells and preserve retinal function in a rodent model of optic nerve injury","volume":"11","author":"Seyedrazizadeh","year":"2020","journal-title":"Stem Cell Res. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Urbanelli, L., Buratta, S., Sagini, K., Tancini, B., and Emiliani, C. (2016). Extracellular Vesicles as New Players in Cellular Senescence. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17091408"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"262","DOI":"10.3389\/fimmu.2020.00262","article-title":"Natural-Killer-Derived Extracellular Vesicles: Immune Sensors and Interactors","volume":"11","author":"Federici","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Groot, M., and Lee, H. (2020). Sorting Mechanisms for MicroRNAs into Extracellular Vesicles and Their Associated Diseases. Cells, 9.","DOI":"10.3390\/cells9041044"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Angelopoulou, E., Paudel, Y.N., Shaikh, M.F., and Piperi, C. (2020). Flotillin: A Promising Biomarker for Alzheimer\u2019s Disease. J. Pers. Med., 10.","DOI":"10.3390\/jpm10020020"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"38","DOI":"10.3389\/fnmol.2020.00038","article-title":"CNS-Derived Blood Exosomes as a Promising Source of Biomarkers: Opportunities and Challenges","volume":"13","author":"Hornung","year":"2020","journal-title":"Front. Mol. Neurosci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"258","DOI":"10.3389\/fnmol.2019.00258","article-title":"The Role of Microglia and Astrocytes in Huntington\u2019s Disease","volume":"12","author":"Palpagama","year":"2019","journal-title":"Front. Mol. Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/s41582-020-0333-7","article-title":"Protein transmission in neurodegenerative disease","volume":"16","author":"Peng","year":"2020","journal-title":"Nat. Rev. Neurol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.brainres.2014.03.042","article-title":"MicroRNA (miRNA): Sequence and stability, viroid-like properties, and disease association in the CNS","volume":"1584","author":"Pogue","year":"2014","journal-title":"Brain Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1134\/S0006297918090031","article-title":"Role of microRNA (miRNA) and Viroids in Lethal Diseases of Plants and Animals. Potential Contribution to Human Neurodegenerative Disorders","volume":"83","author":"Cong","year":"2018","journal-title":"Biochem. (Moscow)"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"S73","DOI":"10.1016\/j.freeradbiomed.2017.04.246","article-title":"Developmental expression and dysregulation of miR146a and miR155 in Down\u2019s syndrome and mouse models of Down\u2019s syndrome and Alzheimer\u2019s disease","volume":"108","author":"Arena","year":"2017","journal-title":"Free. Radic. Boil. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s13293-019-0241-y","article-title":"Sex differences in the expression of cell adhesion molecules on microvesicles derived from cultured human brain microvascular endothelial cells treated with inflammatory and thrombotic stimuli","volume":"10","author":"Hunter","year":"2019","journal-title":"Boil. Sex Differ."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Hosaka, T., Yamashita, T., Tamaoka, A., and Kwak, S. (2019). Extracellular RNAs as Biomarkers of Sporadic Amyotrophic Lateral Sclerosis and Other Neurodegenerative Diseases. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20133148"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/0005-2736(81)90512-5","article-title":"Exfoliation of membrane ecto-enzymes in the form of micro-vesicles","volume":"645","author":"Trams","year":"1981","journal-title":"Biochim. Biophys. Acta (BBA-Biomembr.)"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.neulet.2009.04.052","article-title":"Micro-RNA abundance and stability in human brain: Specific alterations in Alzheimer\u2019s disease temporal lobe neocortex","volume":"459","author":"Sethi","year":"2009","journal-title":"Neurosci. Lett."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Slota, J.A., and Booth, S.A. (2019). MicroRNAs in Neuroinflammation: Implications in Disease Pathogenesis, Biomarker Discovery and Therapeutic Applications. Non-Coding RNA, 5.","DOI":"10.3390\/ncrna5020035"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.3389\/fimmu.2020.01040","article-title":"Modulating Cytokine Production via Select Packaging and Secretion From Extracellular Vesicles","volume":"11","author":"Barnes","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"397","DOI":"10.2217\/epi-2019-0193","article-title":"Radiotherapy-induced overexpression of exosomal miRNA-378a-3p in cancer cells limits natural killer cells cytotoxicity","volume":"12","author":"Briand","year":"2020","journal-title":"Epigenomics"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3187","DOI":"10.1093\/brain\/aww237","article-title":"Exosome secretion is a key pathway for clearance of pathological TDP-43","volume":"139","author":"Iguchi","year":"2016","journal-title":"Brain"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.3389\/fnins.2019.01208","article-title":"miR-212 and miR-132 Are Downregulated in Neurally Derived Plasma Exosomes of Alzheimer\u2019s Patients","volume":"13","author":"Cha","year":"2019","journal-title":"Front. Mol. Neurosci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1159\/000495942","article-title":"Circulating Microparticles in Patients with Symptomatic Carotid Disease Are Related to Embolic Plaque Activity and Recent Cerebral Ischaemia","volume":"9","author":"Kandiyil","year":"2019","journal-title":"Cerebrovasc. Dis. Extra"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Azambuja, J.H., Ludwig, N., Braganhol, E., and Whiteside, T.L. (2019). Inhibition of the Adenosinergic Pathway in Cancer Rejuvenates Innate and Adaptive Immunity. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20225698"},{"key":"ref_47","first-page":"654","article-title":"Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells","volume":"9","author":"Valadi","year":"2007","journal-title":"Nature"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3708","DOI":"10.1111\/jcmm.13671","article-title":"Endothelial microvesicles in hypoxic hypoxia diseases","volume":"22","author":"Deng","year":"2018","journal-title":"J. Cell. Mol. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/s10571-017-0547-4","article-title":"Plant and Animal microRNAs (miRNAs) and Their Potential for Inter-kingdom Communication","volume":"38","author":"Zhao","year":"2017","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Ludwig, N., Azambuja, J.H., Rao, A., Gillespie, D.G., Jackson, E.K., and Whiteside, T.L. (2020). Adenosine receptors regulate exosome production. Purinergic Signal.","DOI":"10.1007\/s11302-020-09700-7"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"81","DOI":"10.3109\/00207459008985953","article-title":"Cytoskeletal Messenger RNA Stability in Human Neocortex: Studies in Normal Aging and in Alzheimer\u2019s Disease","volume":"55","author":"Lukiw","year":"1990","journal-title":"Int. J. Neurosci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1016\/j.expneurol.2011.11.022","article-title":"NF-\u043aB-regulated micro RNAs (miRNAs) in primary human brain cells","volume":"235","author":"Lukiw","year":"2012","journal-title":"Exp. Neurol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"8653","DOI":"10.1523\/JNEUROSCI.1429-16.2016","article-title":"Neutral Sphingomyelinase-2 Deficiency Ameliorates Alzheimer\u2019s Disease Pathology and Improves Cognition in the 5XFAD Mouse","volume":"36","author":"Dinkins","year":"2016","journal-title":"J. Neurosci."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Hill, J.M., Clement, C., Zhao, Y., and Lukiw, W.J. (2015). Induction of the pro-inflammatory NF-kB-sensitive miRNA-146a by human neurotrophic viruses. Front. Microbiol., 6.","DOI":"10.3389\/fmicb.2015.00043"},{"key":"ref_55","first-page":"1470","article-title":"Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers","volume":"10","author":"Skog","year":"2008","journal-title":"Nature"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"811","DOI":"10.3389\/fnagi.2016.00140","article-title":"Over-Expressed Pathogenic miRNAs in Alzheimer\u2019s Disease (AD) and Prion Disease (PrD) Drive Deficits in TREM2-Mediated A\u03b242 Peptide Clearance","volume":"8","author":"Zhao","year":"2016","journal-title":"Front. Aging Neurosci."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Vanherle, S., Haidar, M., Irobi, J., Bogie, J.F., Hendriks, J.J., Jfj, B., and Jja, H. (2020). Extracellular vesicle-associated lipids in central nervous system disorders. Adv. Drug Deliv. Rev.","DOI":"10.1016\/j.addr.2020.04.011"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"211","DOI":"10.5114\/fn.2019.88449","article-title":"Lipopolysaccharide-stimulated, NF-kB-, miRNA-146a- and miRNA-155-mediated molecular-genetic communication between the human gastrointestinal tract microbiome and the brain","volume":"57","author":"Alexandrov","year":"2019","journal-title":"Folia Neuropathol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"9100","DOI":"10.1007\/s12035-018-1015-y","article-title":"Bacteroidetes Neurotoxins and Inflammatory Neurodegeneration","volume":"55","author":"Zhao","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1007\/s00109-017-1545-1","article-title":"Purinergic signaling during intestinal inflammation","volume":"95","author":"Longhi","year":"2017","journal-title":"J. Mol. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"30105","DOI":"10.3390\/ijms161226223","article-title":"MicroRNA (miRNA) Signaling in the Human CNS in Sporadic Alzheimer\u2019s Disease (AD)-Novel and Unique Pathological Features","volume":"16","author":"Zhao","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Fan, W., Liang, C., Ou, M., Zou, T., Sun, F., Zhou, H., and Cui, L. (2020). MicroRNA-146a is a wide-reaching neuroinflammatory regulator and potential treatment target in neurological diseases. Front. Mol. Neurosci.","DOI":"10.3389\/fnmol.2020.00090"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1007\/s10571-017-0572-3","article-title":"Up-regulated Pro-inflammatory MicroRNAs (miRNAs) in Alzheimer\u2019s disease (AD) and Age-Related Macular Degeneration (AMD)","volume":"38","author":"Pogue","year":"2018","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.bcp.2017.12.020","article-title":"Microglia-derived extracellular vesicles in Alzheimer\u2019s Disease: A double-edged sword","volume":"148","author":"Trotta","year":"2018","journal-title":"Biochem. Pharmacol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1002\/glia.23846","article-title":"Regulatory function of microRNAs in microglia","volume":"68","author":"Brites","year":"2020","journal-title":"Glia"},{"key":"ref_66","first-page":"69","article-title":"Anti-microRNAs as Novel Therapeutic Agents in the Clinical Management of Alzheimer\u2019s Disease","volume":"10","author":"Zhao","year":"2016","journal-title":"Front. Mol. Neurosci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/0169-328X(88)90048-4","article-title":"Selective messenger RNA reduction in Alzheimer\u2019s disease","volume":"3","author":"McLachlan","year":"1988","journal-title":"Mol. Brain Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"508","DOI":"10.2174\/1570159X15666170720095240","article-title":"Microglia and Astrocytes in Alzheimer\u2019s Disease: Implications for Therapy","volume":"16","author":"Fakhoury","year":"2018","journal-title":"Curr. Neuropharmacol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2174\/1389557520666200513122357","article-title":"A Systematic Review of Current Progresses in The Nucleic Acid-Based Therapies for Neurodegeneration with Implications for Alzheimer\u2019s disease","volume":"20","author":"Ghaffari","year":"2020","journal-title":"Mini-Reviews Med. Chem."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Lukiw, W.J., Cong, L., Jaber, V., and Zhao, Y. (2018). Microbiome-Derived Lipopolysaccharide (LPS) Selectively Inhibits Neurofilament Light Chain (NF-L) Gene Expression in Human Neuronal-Glial (HNG) Cells in Primary Culture. Front. Mol. Neurosci., 12.","DOI":"10.3389\/fnins.2018.00896"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.addr.2015.05.001","article-title":"An overview of microRNAs","volume":"87","author":"Hammond","year":"2015","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"3329","DOI":"10.12659\/MSM.914027","article-title":"Exosomes in Pathogenesis, Diagnosis, and Treatment of Alzheimer\u2019s Disease","volume":"25","author":"Jiang","year":"2019","journal-title":"Med Sci. Monit."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.4103\/1673-5374.270302","article-title":"Exosome-mediated crosstalk between microglia and neural stem cells in the repair of brain injury","volume":"15","author":"Hou","year":"2020","journal-title":"Neural Regen. Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.neuroscience.2020.02.044","article-title":"Profile of Pathogenic Proteins and MicroRNAs in Plasma-derived Extracellular Vesicles in Alzheimer\u2019s Disease: A Pilot Study","volume":"432","author":"Li","year":"2020","journal-title":"Neuroscience"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"110251","DOI":"10.1016\/j.biopha.2020.110251","article-title":"CircRNAs: A new perspective of biomarkers in the nervous system","volume":"128","author":"Ma","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Lukiw, W.J. (2013). Circular RNA (circRNA) in Alzheimer\u2019s disease (AD). Front. Genet., 4.","DOI":"10.3389\/fgene.2013.00307"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/alzrt150","article-title":"NF-\u03baB-regulated, proinflammatory miRNAs in Alzheimer\u2019s disease","volume":"4","author":"Lukiw","year":"2012","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Zhao, Y., Alexandrov, P.N., Jaber, V., and Lukiw, W.J. (2016). Deficiency in the Ubiquitin Conjugating Enzyme UBE2A in Alzheimer\u2019s Disease (AD) is Linked to Deficits in a Natural Circular miRNA-7 Sponge (circRNA; ciRS-7). Genes, 7.","DOI":"10.3390\/genes7120116"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Lukiw, W.J. (2020). microRNA-146a signaling in Alzheimer\u2019s disease (AD) and prion disease (PrD). Front. Neurol.","DOI":"10.3389\/fneur.2020.00462"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/14\/5078\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:49:38Z","timestamp":1760176178000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/14\/5078"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,18]]},"references-count":79,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2020,7]]}},"alternative-id":["ijms21145078"],"URL":"https:\/\/doi.org\/10.3390\/ijms21145078","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,18]]}}}