{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T21:26:33Z","timestamp":1776374793045,"version":"3.51.2"},"reference-count":136,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2022,10,26]],"date-time":"2022-10-26T00:00:00Z","timestamp":1666742400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT)","award":["JPco-fuND\/0003\/2015"],"award-info":[{"award-number":["JPco-fuND\/0003\/2015"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT)","award":["PTDC\/MED-NEU\/31395\/2017"],"award-info":[{"award-number":["PTDC\/MED-NEU\/31395\/2017"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT)","award":["PTDC\/MED-NEU\/2382\/2021"],"award-info":[{"award-number":["PTDC\/MED-NEU\/2382\/2021"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT)","award":["LISBOA-01-0145-FEDER-031395"],"award-info":[{"award-number":["LISBOA-01-0145-FEDER-031395"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT)","award":["PTDC\/MED-NEU\/27946\/2017"],"award-info":[{"award-number":["PTDC\/MED-NEU\/27946\/2017"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT)","award":["UID\/DTP\/04138\/2019"],"award-info":[{"award-number":["UID\/DTP\/04138\/2019"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT)","award":["UIDB\/04138\/2020"],"award-info":[{"award-number":["UIDB\/04138\/2020"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT)","award":["UIDP\/04138\/2020"],"award-info":[{"award-number":["UIDP\/04138\/2020"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT)","award":["SFRH\/BD\/128738\/2017"],"award-info":[{"award-number":["SFRH\/BD\/128738\/2017"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT)","award":["COVID\/BD\/151849\/2021"],"award-info":[{"award-number":["COVID\/BD\/151849\/2021"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is a neurodegenerative disorder associated with neuron\u2013glia dysfunction and dysregulated miRNAs. We previously reported upregulated miR-124\/miR-21 in AD neurons and their exosomes. However, their glial distribution, phenotypic alterations and exosomal spread are scarcely documented. Here, we show glial cell activation and miR-21 overexpression in mouse organotypic hippocampal slices transplanted with SH-SY5Y cells expressing the human APP695 Swedish mutation. The upregulation of miR-21 only in the CSF from a small series of mild cognitive impairment (MCI) AD patients, but not in non-AD MCI individuals, supports its discriminatory potential. Microglia, neurons, and astrocytes differentiated from the same induced pluripotent stem cells from PSEN1\u0394E9 AD patients all showed miR-21 elevation. In AD neurons, miR-124\/miR-21 overexpression was recapitulated in their exosomes. In AD microglia, the upregulation of iNOS and miR-21\/miR-146a supports their activation. AD astrocytes manifested a restrained inflammatory profile, with high miR-21 but low miR-155 and depleted exosomal miRNAs. Their immunostimulation with C1q + IL-1\u03b1 + TNF-\u03b1 induced morphological alterations and increased S100B, inflammatory transcripts, sAPP\u03b2, cytokine release and exosomal miR-21. PPAR\u03b1, a target of miR-21, was found to be repressed in all models, except in neurons, likely due to concomitant miR-125b elevation. The data from these AD models highlight miR-21 as a promising biomarker and a disease-modifying target to be further explored.<\/jats:p>","DOI":"10.3390\/cells11213377","type":"journal-article","created":{"date-parts":[[2022,10,26]],"date-time":"2022-10-26T07:17:48Z","timestamp":1666768668000},"page":"3377","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Emerging Role of miR-21-5p in Neuron\u2013Glia Dysregulation and Exosome Transfer Using Multiple Models of Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5526-5362","authenticated-orcid":false,"given":"Gon\u00e7alo","family":"Garcia","sequence":"first","affiliation":[{"name":"Neuroinflammation, Signaling and Neuroregeneration Lab, Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal"},{"name":"Department of Pharmaceutical Sciences and Medicines, Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal"}]},{"given":"Sara","family":"Pinto","sequence":"additional","affiliation":[{"name":"Neuroinflammation, Signaling and Neuroregeneration Lab, Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal"},{"name":"Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal"}]},{"given":"Sofia","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Neuroinflammation, Signaling and Neuroregeneration Lab, Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal"}]},{"given":"Daniela","family":"Lopes","sequence":"additional","affiliation":[{"name":"Neuroinflammation, Signaling and Neuroregeneration Lab, Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal"}]},{"given":"Maria Jo\u00e3o","family":"Serrador","sequence":"additional","affiliation":[{"name":"Neuroinflammation, Signaling and Neuroregeneration Lab, Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2782-9519","authenticated-orcid":false,"given":"Adelaide","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences and Medicines, Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal"},{"name":"Central Nervous System, Blood and Peripheral Inflammation Lab, Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3418-3269","authenticated-orcid":false,"given":"Ana Rita","family":"Vaz","sequence":"additional","affiliation":[{"name":"Neuroinflammation, Signaling and Neuroregeneration Lab, Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal"},{"name":"Department of Pharmaceutical Sciences and Medicines, Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0488-1453","authenticated-orcid":false,"given":"Alexandre de","family":"Mendon\u00e7a","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Universidade de Lisboa, 1649-028 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6489-714X","authenticated-orcid":false,"given":"Frank","family":"Edenhofer","sequence":"additional","affiliation":[{"name":"Department of Genomics, Stem Cell Biology and Regenerative Medicine, Center for Molecular Biosciences, University of Innsbruck, 6020 Innsbruck, Austria"}]},{"given":"Tarja","family":"Malm","sequence":"additional","affiliation":[{"name":"A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70211 Kuopio, Finland"}]},{"given":"Jari","family":"Koistinaho","sequence":"additional","affiliation":[{"name":"A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70211 Kuopio, Finland"},{"name":"Neuroscience Center, Helsinki Institute of Life Science (HiLIFE), University of Helsinki, 00014 Helsinki, Finland"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3024-9777","authenticated-orcid":false,"given":"Dora","family":"Brites","sequence":"additional","affiliation":[{"name":"Neuroinflammation, Signaling and Neuroregeneration Lab, Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal"},{"name":"Department of Pharmaceutical Sciences and Medicines, Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"323","DOI":"10.3233\/JAD-190426","article-title":"Tip of the Iceberg: Assessing the Global Socioeconomic Costs of Alzheimer\u2019s Disease and Related Dementias and Strategic Implications for Stakeholders","volume":"70","author":"Wiley","year":"2019","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0140-6736(18)31896-8","article-title":"Unsuccessful Trials of Therapies for Alzheimer\u2019s Disease","volume":"393","author":"Schott","year":"2019","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e12295","DOI":"10.1002\/trc2.12295","article-title":"Alzheimer\u2019s Disease Drug Development Pipeline: 2022","volume":"8","author":"Cummings","year":"2022","journal-title":"Alzheimer\u2019s Dement. Transl. Res. Clin. Interv."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"221","DOI":"10.3233\/JAD-2010-1220","article-title":"Neuropathologic Alterations in Mild Cognitive Impairment: A Review","volume":"19","author":"Markesbery","year":"2010","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.jalz.2011.03.008","article-title":"The Diagnosis of Mild Cognitive Impairment Due to Alzheimer\u2019s Disease: Recommendations from the National Institute on Aging-Alzheimer\u2019s Association Workgroups on Diagnostic Guidelines for Alzheimer\u2019s Disease","volume":"7","author":"Albert","year":"2011","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Zou, K., Abdullah, M., and Michikawa, M. (2020). Current Biomarkers for Alzheimer\u2019s Disease: From CSF to Blood. J. Pers. Med., 10.","DOI":"10.3390\/jpm10030085"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s40035-022-00296-z","article-title":"Advances in the Development of New Biomarkers for Alzheimer\u2019s Disease","volume":"11","author":"Klyucherev","year":"2022","journal-title":"Transl. Neurodegener."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1038\/s41586-022-04640-1","article-title":"Somatic Genomic Changes in Single Alzheimer\u2019s Disease Neurons","volume":"604","author":"Miller","year":"2022","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/j.cell.2015.12.056","article-title":"The Cellular Phase of Alzheimer\u2019s Disease","volume":"164","author":"Karran","year":"2016","journal-title":"Cell"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Preman, P., Alfonso-Triguero, M., Alberdi, E., Verkhratsky, A., and Arranz, A.M. (2021). Astrocytes in Alzheimer\u2019s Disease: Pathological Significance and Molecular Pathways. Cells, 10.","DOI":"10.20944\/preprints202102.0230.v1"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"427","DOI":"10.3389\/fnmol.2017.00427","article-title":"Involvement of Astrocytes in Alzheimer\u2019s Disease from a Neuroinflammatory and Oxidative Stress Perspective","volume":"10","year":"2017","journal-title":"Front. Mol. Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"5312","DOI":"10.1523\/JNEUROSCI.5274-12.2013","article-title":"Amyloid- 1-42 Slows Clearance of Synaptically Released Glutamate by Mislocalizing Astrocytic GLT-1","volume":"33","author":"Scimemi","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1002\/glia.20967","article-title":"Concomitant Astroglial Atrophy and Astrogliosis in a Triple Transgenic Animal Model of Alzheimer\u2019s Disease","volume":"58","author":"Olabarria","year":"2010","journal-title":"Glia"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/S1474-4422(15)70016-5","article-title":"Neuroinflammation in Alzheimer\u2019s Disease","volume":"14","author":"Heneka","year":"2015","journal-title":"Lancet Neurol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2665","DOI":"10.1523\/JNEUROSCI.23-07-02665.2003","article-title":"A Cell Surface Receptor Complex for Fibrillar \u03b2-Amyloid Mediates Microglial Activation","volume":"23","author":"Bamberger","year":"2003","journal-title":"J. Neurosci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1083\/jcb.201709069","article-title":"Microglia in Alzheimer\u2019s Disease","volume":"217","author":"Hansen","year":"2018","journal-title":"J. Cell Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"8354","DOI":"10.1523\/JNEUROSCI.0616-08.2008","article-title":"Microglial Dysfunction and Defective -Amyloid Clearance Pathways in Aging Alzheimer\u2019s Disease Mice","volume":"28","author":"Hickman","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1111\/jnc.13411","article-title":"The Contribution of Neuroinflammation to Amyloid Toxicity in Alzheimer\u2019s Disease","volume":"136","author":"Minter","year":"2016","journal-title":"J. Neurochem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1007\/s00401-016-1662-x","article-title":"Alzheimer\u2019s Disease: Experimental Models and Reality","volume":"133","author":"Drummond","year":"2017","journal-title":"Acta Neuropathol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2766","DOI":"10.3389\/fmicb.2018.02766","article-title":"Microglia Increase Inflammatory Responses in IPSC-Derived Human BrainSpheres","volume":"9","author":"Abreu","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.neuron.2017.03.042","article-title":"IPSC-Derived Human Microglia-like Cells to Study Neurological Diseases","volume":"94","author":"Abud","year":"2017","journal-title":"Neuron"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1016\/j.stemcr.2018.03.003","article-title":"Functional Studies of Missense TREM2 Mutations in Human Stem Cell-Derived Microglia","volume":"10","author":"Brownjohn","year":"2018","journal-title":"Stem. Cell Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.reth.2020.11.006","article-title":"IPSC for Modeling Neurodegenerative Disorders","volume":"15","year":"2020","journal-title":"Regen. Ther."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"7828049","DOI":"10.1155\/2016\/7828049","article-title":"Modeling Alzheimer\u2019s Disease with Induced Pluripotent Stem Cells: Current Challenges and Future Concerns","volume":"2016","author":"Zhang","year":"2016","journal-title":"Stem Cells Int."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Garcia, G., Pinto, S., Cunha, M., Fernandes, A., Koistinaho, J., and Brites, D. (2021). Neuronal Dynamics and MiRNA Signaling Differ between SH-SY5Y APPSwe and PSEN1 Mutant IPSC-Derived AD Models upon Modulation with MiR-124 Mimic and Inhibitor. Cells, 10.","DOI":"10.3390\/cells10092424"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/j.stemcr.2019.08.004","article-title":"PSEN1\u0394E9, APPswe, and APOE4 Confer Disparate Phenotypes in Human IPSC-Derived Microglia","volume":"13","author":"Konttinen","year":"2019","journal-title":"Stem Cell Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.1016\/j.stemcr.2017.10.016","article-title":"PSEN1 Mutant IPSC-Derived Model Reveals Severe Astrocyte Pathology in Alzheimer\u2019s Disease","volume":"9","author":"Oksanen","year":"2017","journal-title":"Stem Cell Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e2696","DOI":"10.1038\/cddis.2017.89","article-title":"Aberrant IPSC-Derived Human Astrocytes in Alzheimer\u2019s Disease","volume":"8","author":"Jones","year":"2017","journal-title":"Cell Death Dis."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Zhang, Z., Almeida, S., Lu, Y., Nishimura, A.L., Peng, L., Sun, D., Wu, B., Karydas, A.M., Tartaglia, M.C., and Fong, J.C. (2013). Downregulation of MicroRNA-9 in IPSC-Derived Neurons of FTD\/ALS Patients with TDP-43 Mutations. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0076055"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.neurobiolaging.2018.09.011","article-title":"MiR-125b Promotes Tau Phosphorylation by Targeting the Neural Cell Adhesion Molecule in Neuropathological Progression","volume":"73","author":"Zhang","year":"2019","journal-title":"Neurobiol. Aging"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3445","DOI":"10.1038\/s41598-019-38910-2","article-title":"MiR-124 Dosage Regulates Prefrontal Cortex Function by Dopaminergic Modulation","volume":"9","author":"Kozuka","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Schonrock, N., Ke, Y.D., Humphreys, D., Staufenbiel, M., Ittner, L.M., Preiss, T., and G\u00f6tz, J. (2010). Neuronal MicroRNA Deregulation in Response to Alzheimer\u2019s Disease Amyloid-\u03b2. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0011070"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s40364-021-00272-1","article-title":"MiR-21: A Non-specific Biomarker of All Maladies","volume":"9","author":"Jenike","year":"2021","journal-title":"Biomark. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5","DOI":"10.3389\/fnmol.2022.842288","article-title":"MicroRNA-21 Is a Versatile Regulator and Potential Treatment Target in Central Nervous System Disorders","volume":"15","author":"Bai","year":"2022","journal-title":"Front. Mol. Neurosci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1016\/j.biopha.2018.02.043","article-title":"MiR-21 Attenuates Apoptosis-Triggered by Amyloid-\u03b2 via Modulating PDCD4\/ PI3K\/AKT\/GSK-3\u03b2 Pathway in SH-SY5Y Cells","volume":"101","author":"Feng","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Burgos, K., Malenica, I., Metpally, R., Courtright, A., Rakela, B., Beach, T., Shill, H., Adler, C., Sabbagh, M., and Villa, S. (2014). Profiles of Extracellular MiRNA in Cerebrospinal Fluid and Serum from Patients with Alzheimer\u2019s and Parkinson\u2019s Diseases Correlate with Disease Status and Features of Pathology. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0094839"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"108","DOI":"10.3389\/fnagi.2021.647015","article-title":"Circulating Inflamma-MiRs as Potential Biomarkers of Cognitive Impairment in Patients Affected by Alzheimer\u2019s Disease","volume":"13","author":"Giuliani","year":"2021","journal-title":"Front. Aging Neurosci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"273","DOI":"10.3389\/fnins.2017.00273","article-title":"Exosomes from NSC-34 Cells Transfected with HSOD1-G93A Are Enriched in Mir-124 and Drive Alterations in Microglia Phenotype","volume":"11","author":"Pinto","year":"2017","journal-title":"Front. Neurosci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.biochi.2018.05.015","article-title":"Secretome from SH-SY5Y APPSwe Cells Trigger Time-Dependent CHME3 Microglia Activation Phenotypes, Ultimately Leading to MiR-21 Exosome Shuttling","volume":"155","author":"Fernandes","year":"2018","journal-title":"Biochimie"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.3389\/fphar.2022.833066","article-title":"Protective Signature of IFN\u03b3-Stimulated Microglia Relies on MiR-124-3p Regulation from the Secretome Released by Mutant APP Swedish Neuronal Cells","volume":"13","author":"Garcia","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Barbosa, M., Santos, M., de Sousa, N., Duarte-Silva, S., Vaz, A.R., Salgado, A.J., and Brites, D. (2022). Intrathecal Injection of the Secretome from ALS Motor Neurons Regulated for MiR-124 Expression Prevents Disease Outcomes in SOD1-G93A Mice. Biomedicines, 10.","DOI":"10.3390\/biomedicines10092120"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"443","DOI":"10.3389\/fncel.2021.785433","article-title":"Inflamma-MicroRNAs in Alzheimer\u2019s Disease: From Disease Pathogenesis to Therapeutic Potentials","volume":"15","author":"Liang","year":"2021","journal-title":"Front. Cell Neurosci."},{"key":"ref_43","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_44","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/nature21029","article-title":"Neurotoxic Reactive Astrocytes Are Induced by Activated Microglia","volume":"541","author":"Liddelow","year":"2017","journal-title":"Nature"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2398","DOI":"10.1016\/j.neuropharm.2012.02.002","article-title":"Neuritic Growth Impairment and Cell Death by Unconjugated Bilirubin Is Mediated by NO and Glutamate, Modulated by Microglia, and Prevented by Glycoursodeoxycholic Acid and Interleukin-10","volume":"62","author":"Silva","year":"2012","journal-title":"Neuropharmacology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"143","DOI":"10.3389\/fncel.2017.00143","article-title":"Differentiation of Human Induced Pluripotent Stem Cell (HiPSC)-Derived Neurons in Mouse Hippocampal Slice Cultures","volume":"11","author":"Hiragi","year":"2017","journal-title":"Front. Cell Neurosci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/0022-3956(75)90026-6","article-title":"\u201cMini-Mental State\u201d. A Practical Method for Grading the Cognitive State of Patients for the Clinician","volume":"12","author":"Folstein","year":"1975","journal-title":"J. Psychiatr. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2412","DOI":"10.1212\/WNL.43.11.2412-a","article-title":"The Clinical Dementia Rating (CDR): Current Version and Scoring Rules","volume":"43","author":"Morris","year":"1993","journal-title":"Neurology"},{"key":"ref_49","first-page":"111","article-title":"Consensus Guidelines for Lumbar Puncture in Patients with Neurological Diseases","volume":"8","author":"Engelborghs","year":"2017","journal-title":"Alzheimer\u2019s Dement. Diagn. Assess. Dis. Monit."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.clinbiochem.2013.12.024","article-title":"Biobanking of CSF: International Standardization to Optimize Biomarker Development","volume":"47","author":"Teunissen","year":"2014","journal-title":"Clin. Biochem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1038\/nbt.1529","article-title":"Highly Efficient Neural Conversion of Human ES and IPS Cells by Dual Inhibition of SMAD Signaling","volume":"27","author":"Chambers","year":"2009","journal-title":"Nat. Biotechnol"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1710","DOI":"10.1038\/nprot.2011.405","article-title":"Directed Differentiation of Functional Astroglial Subtypes from Human Pluripotent Stem Cells","volume":"6","author":"Krencik","year":"2011","journal-title":"Nat. Protoc."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: An Open-Source Platform for Biological-Image Analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Method."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"152","DOI":"10.3389\/fncel.2014.00152","article-title":"Microglia Change from a Reactive to an Age-like Phenotype with the Time in Culture","volume":"8","author":"Caldeira","year":"2014","journal-title":"Front. Cell. Neurosci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"E3679","DOI":"10.1073\/pnas.1617259114","article-title":"Defective Synaptic Connectivity and Axonal Neuropathology in a Human IPSC-Based Model of Familial Parkinson\u2019s Disease","volume":"114","author":"Kouroupi","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"109","DOI":"10.3389\/fncel.2019.00109","article-title":"Phenotypic Effects of Wild-Type and Mutant SOD1 Expression in N9 Murine Microglia at Steady State, Inflammatory and Immunomodulatory Conditions","volume":"13","author":"Vaz","year":"2019","journal-title":"Front. Cell. Neurosci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s12640-013-9427-y","article-title":"Cross-Talk between Neurons and Astrocytes in Response to Bilirubin: Adverse Secondary Impacts","volume":"26","author":"Silva","year":"2014","journal-title":"Neurotox. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"65","DOI":"10.4103\/1673-5374.243704","article-title":"Using Organotypic Hippocampal Slice Cultures to Gain Insight into Mechanisms Responsible for the Neuroprotective Effects of Meloxicam: A Role for Gamma Aminobutyric and Endoplasmic Reticulum Stress","volume":"14","author":"Landucci","year":"2019","journal-title":"Neural. Regen. Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1016\/j.stemcr.2019.10.012","article-title":"Human Neural Stem Cells Reinforce Hippocampal Synaptic Network and Rescue Cognitive Deficits in a Mouse Model of Alzheimer\u2019s Disease","volume":"13","author":"Zhang","year":"2019","journal-title":"Stem Cell Rep."},{"key":"ref_60","first-page":"5878","article-title":"MicroRNA-21-5p Promotes the Inflammatory Response after Spinal Cord Injury by Targeting PLAG1","volume":"24","author":"Han","year":"2020","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.bbi.2019.11.004","article-title":"Neuron-Derived Exosomes with High MiR-21-5p Expression Promoted Polarization of M1 Microglia in Culture","volume":"83","author":"Yin","year":"2020","journal-title":"Brain Behav. Immun."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Yelamanchili, S.V., Lamberty, B.G., Rennard, D.A., Morsey, B.M., Hochfelder, C.G., Meays, B.M., Levy, E., and Fox, H.S. (2015). MiR-21 in Extracellular Vesicles Leads to Neurotoxicity via TLR7 Signaling in SIV Neurological Disease. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1005131"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Liu, Y., Yang, X., Guo, C., Nie, P., Liu, Y., and Ma, J. (2013). Essential Role of MFG-E8 for Phagocytic Properties of Microglial Cells. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0055754"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1007\/s11481-008-9118-2","article-title":"MFG-E8 Regulates Microglial Phagocytosis of Apoptotic Neurons","volume":"3","author":"Fuller","year":"2008","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.stemcr.2020.06.001","article-title":"Human IPSC-Derived Hippocampal Spheroids: An Innovative Tool for Stratifying Alzheimer Disease Patient-Specific Cellular Phenotypes and Developing Therapies","volume":"15","author":"Pomeshchik","year":"2020","journal-title":"Stem Cell Rep."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"17935","DOI":"10.1523\/JNEUROSCI.3860-12.2012","article-title":"MicroRNA-21 Regulates Astrocytic Response Following Spinal Cord Injury","volume":"32","author":"Bhalala","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.neuropharm.2018.04.028","article-title":"Inhibition of MiR-21 Ameliorates Excessive Astrocyte Activation and Promotes Axon Regeneration Following Optic Nerve Crush","volume":"137","author":"Li","year":"2018","journal-title":"Neuropharmacology"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2251","DOI":"10.1007\/s00259-022-05682-3","article-title":"Clozapine Induces Astrocyte-Dependent FDG-PET Hypometabolism","volume":"49","author":"Rocha","year":"2022","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.molmed.2018.11.006","article-title":"Astrocyte Biomarkers in Alzheimer\u2019s Disease","volume":"25","author":"Carter","year":"2019","journal-title":"Trends Mol. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1186\/s12974-022-02565-0","article-title":"Astrocytic and Microglial Cells as the Modulators of Neuroinflammation in Alzheimer\u2019s Disease","volume":"19","author":"Singh","year":"2022","journal-title":"J. Neuroinflamm."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1038\/s41582-020-00435-y","article-title":"Neuroinflammation and Microglial Activation in Alzheimer Disease: Where Do We Go from Here?","volume":"17","author":"Leng","year":"2021","journal-title":"Nat. Rev. Neurol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"622","DOI":"10.3389\/fnins.2018.00622","article-title":"Dysregulation of Astrocytic HMGB1 Signaling in Amyotrophic Lateral Sclerosis","volume":"12","author":"Brambilla","year":"2018","journal-title":"Front. Neurosci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.kint.2017.05.014","article-title":"MicroRNA-21 Regulates Peroxisome Proliferator\u2013Activated Receptor Alpha, a Molecular Mechanism of Cardiac Pathology in Cardiorenal Syndrome Type 4","volume":"93","author":"Chuppa","year":"2018","journal-title":"Kidney Int."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e150099","DOI":"10.1172\/jci.insight.150099","article-title":"Regulation of PPAR\u03b1 by APP in Alzheimer Disease Affects the Pharmacological Modulation of Synaptic Activity","volume":"6","author":"Leroy","year":"2021","journal-title":"JCI Insight"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"eabg4747","DOI":"10.1126\/scisignal.abg4747","article-title":"Activation of PPAR\u03b1 Enhances Astroglial Uptake and Degradation of \u03b2-Amyloid","volume":"14","author":"Raha","year":"2021","journal-title":"Sci. Signal"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"288","DOI":"10.3389\/fneur.2020.00288","article-title":"The Regulation of MicroRNAs in Alzheimer\u2019s Disease","volume":"11","author":"Kou","year":"2020","journal-title":"Front. Neurol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/s13024-021-00496-7","article-title":"The Promise of MicroRNA-Based Therapies in Alzheimer\u2019s Disease: Challenges and Perspectives","volume":"16","author":"Walgrave","year":"2021","journal-title":"Mol. Neurodegener."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"160","DOI":"10.3389\/fnmol.2020.00160","article-title":"MicroRNAs in Alzheimer\u2019s Disease: Function and Potential Applications as Diagnostic Biomarkers","volume":"13","author":"Wei","year":"2020","journal-title":"Front. Mol. Neurosci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.1038\/s41591-021-01456-w","article-title":"Microglial Activation and Tau Propagate Jointly across Braak Stages","volume":"27","author":"Pascoal","year":"2021","journal-title":"Nat. Med."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Gentile, G., Morello, G., La Cognata, V., Guarnaccia, M., Conforti, F.L., and Cavallaro, S. (2022). Dysregulated MiRNAs as Biomarkers and Therapeutical Targets in Neurodegenerative Diseases. J. Pers. Med., 12.","DOI":"10.3390\/jpm12050770"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"112681","DOI":"10.1016\/j.biopha.2022.112681","article-title":"MicroRNAs in Alzheimer\u2019s Disease: Potential Diagnostic Markers and Therapeutic Targets","volume":"148","author":"Liu","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Vaz, A.R., Vizinha, D., Morais, H., Cola\u00e7o, A.R., Loch-Neckel, G., Barbosa, M., and Brites, D. (2021). Overexpression of MiR-124 in Motor Neurons Plays a Key Role in ALS Pathological Processes. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22116128"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"930","DOI":"10.3389\/fcell.2021.634355","article-title":"Recovery of Depleted MiR-146a in ALS Cortical Astrocytes Reverts Cell Aberrancies and Prevents Paracrine Pathogenicity on Microglia and Motor Neurons","volume":"9","author":"Barbosa","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Gomes, C., Sequeira, C., Likhite, S., Dennys, C.N., Kolb, S.J., Shaw, P.J., Vaz, A.R., Kaspar, B.K., Meyer, K., and Brites, D. (2022). Neurotoxic Astrocytes Directly Converted from Sporadic and Familial ALS Patient Fibroblasts Reveal Signature Diversities and MiR-146a Theragnostic Potential in Specific Subtypes. Cells, 11.","DOI":"10.3390\/cells11071186"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"19","DOI":"10.2174\/157015907780077105","article-title":"Brain Slices as Models for Neurodegenerative Disease and Screening Platforms to Identify Novel Therapeutics","volume":"5","author":"Cho","year":"2007","journal-title":"Curr. Neuropharmacol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.3389\/fnins.2018.01053","article-title":"Glutamate Receptor-Mediated Neurotoxicity in a Model of Ethanol Dependence and Withdrawal in Rat Organotypic Hippocampal Slice Cultures","volume":"12","author":"Gerace","year":"2019","journal-title":"Front. Neurosci."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"113","DOI":"10.3389\/fnagi.2018.00113","article-title":"Differential Hyperphosphorylation of Tau-S199, -T231 and -S396 in Organotypic Brain Slices of Alzheimer Mice. A Model to Study Early Tau Hyperphosphorylation Using Okadaic Acid","volume":"10","author":"Foidl","year":"2018","journal-title":"Front. Aging Neurosci."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"205","DOI":"10.30773\/pi.2017.04.02","article-title":"Long-Term Culture of Organotypic Hippocampal Slice from Old 3xTg-AD Mouse: An Ex Vivo Model of Alzheimer\u2019s Disease","volume":"15","author":"Jang","year":"2018","journal-title":"Psychiatry Investig."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"444","DOI":"10.3389\/fncel.2020.592005","article-title":"Organotypic Brain Slice Culture Microglia Exhibit Molecular Similarity to Acutely-Isolated Adult Microglia and Provide a Platform to Study Neuroinflammation","volume":"14","author":"Delbridge","year":"2020","journal-title":"Front. Cell Neurosci."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"114","DOI":"10.3389\/fnagi.2018.00114","article-title":"Deciphering the Astrocyte Reaction in Alzheimer\u2019s Disease","volume":"10","year":"2018","journal-title":"Front. Aging Neurosci."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1007\/s12010-017-2468-6","article-title":"Evaluation of the Expression of Amyloid Precursor Protein and the Ratio of Secreted Amyloid Beta 42 to Amyloid Beta 40 in SH-SY5Y Cells Stably Transfected with Wild-Type, Single-Mutant and Double-Mutant Forms of the APP Gene for the Study of Alzheimer\u2019s Disease Pathology","volume":"183","author":"Shukri","year":"2017","journal-title":"Appl. Biochem. Biotechnol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.neuro.2022.07.008","article-title":"The SH-SY5Y Human Neuroblastoma Cell Line, a Relevant in Vitro Cell Model for Investigating Neurotoxicology in Human: Focus on Organic Pollutants","volume":"92","author":"Awabdh","year":"2022","journal-title":"Neurotoxicology"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1038\/s41380-019-0468-3","article-title":"Modeling Alzheimer\u2019s Disease with IPSC-Derived Brain Cells","volume":"25","author":"Penney","year":"2020","journal-title":"Mol. Psychiatry"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/978-1-62703-640-5_2","article-title":"Considerations for the Use of SH-SY5Y Neuroblastoma Cells in Neurobiology","volume":"Volume 1078","author":"Kovalevich","year":"2013","journal-title":"Methods in Molecular Biology (Clifton, N.J.)"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s13024-017-0149-0","article-title":"The SH-SY5Y Cell Line in Parkinson\u2019s Disease Research: A Systematic Review","volume":"12","author":"Xicoy","year":"2017","journal-title":"Mol. Neurodegener."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1186\/s12974-019-1590-5","article-title":"Analysis of MiRNA Signatures in CSF Identifies Upregulation of MiR-21 and MiR-146a\/b in Patients with Multiple Sclerosis and Active Lesions","volume":"16","author":"Reverter","year":"2019","journal-title":"J. Neuroinflamm."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s40035-019-0169-5","article-title":"Exploratory Study on MicroRNA Profiles from Plasma-Derived Extracellular Vesicles in Alzheimer\u2019s Disease and Dementia with Lewy Bodies","volume":"8","author":"Campdelacreu","year":"2019","journal-title":"Transl. Neurodegener."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s40035-016-0053-5","article-title":"MiRNA Expression Profiles in Cerebrospinal Fluid and Blood of Patients with Alzheimer\u2019s Disease and Other Types of Dementia\u2014An Exploratory Study","volume":"5","author":"Nygaard","year":"2016","journal-title":"Transl. Neurodegener."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s40035-019-0161-0","article-title":"Alzheimer\u2019s in a Dish\u2014Induced Pluripotent Stem Cell-Based Disease Modeling","volume":"8","author":"Tackenberg","year":"2019","journal-title":"Transl. Neurodegener."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/nature10821","article-title":"Probing Sporadic and Familial Alzheimer\u2019s Disease Using Induced Pluripotent Stem Cells","volume":"482","author":"Israel","year":"2012","journal-title":"Nature"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s13024-016-0106-3","article-title":"Induced Pluripotent Stem Cells in Alzheimer\u2019s Disease: Applications for Disease Modeling and Cell-Replacement Therapy","volume":"11","author":"Yang","year":"2016","journal-title":"Mol. Neurodegener."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1038\/s42003-021-02276-x","article-title":"Resolving Cell State in IPSC-Derived Human Neural Samples with Multiplexed Fluorescence Imaging","volume":"4","author":"Tomov","year":"2021","journal-title":"Commun. Biol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1038\/nm.4189","article-title":"Efficient Derivation of Microglia-like Cells from Human Pluripotent Stem Cells","volume":"22","author":"Muffat","year":"2016","journal-title":"Nat. Med."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"3918","DOI":"10.3389\/fimmu.2020.617860","article-title":"Alzheimer\u2019s Risk Gene TREM2 Determines Functional Properties of New Type of Human IPSC-Derived Microglia","volume":"11","author":"Reich","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"3376","DOI":"10.3389\/fimmu.2020.582998","article-title":"Arginase 1 Insufficiency Precipitates Amyloid-\u03b2 Deposition and Hastens Behavioral Impairment in a Mouse Model of Amyloidosis","volume":"11","author":"Ma","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1523\/JNEUROSCI.21-04-01179.2001","article-title":"\u03b2-Amyloid Stimulation of Microglia and Monocytes Results in TNF\u03b1-Dependent Expression of Inducible Nitric Oxide Synthase and Neuronal Apoptosis","volume":"21","author":"Combs","year":"2001","journal-title":"J. Neurosci."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1186\/s12974-015-0411-8","article-title":"Arginase 1+ Microglia Reduce A\u03b2 Plaque Deposition during IL-1\u03b2-Dependent Neuroinflammation","volume":"12","author":"Cherry","year":"2015","journal-title":"J. Neuroinflamm."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.neuroscience.2014.09.050","article-title":"What Happens to Microglial TREM2 in Alzheimer\u2019s Disease: Immunoregulatory Turned into Immunopathogenic?","volume":"302","author":"Lue","year":"2015","journal-title":"Neuroscience"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"4103","DOI":"10.7150\/thno.53418","article-title":"MicroRNA-146a Switches Microglial Phenotypes to Resist the Pathological Processes and Cognitive Degradation of Alzheimer\u2019s Disease","volume":"11","author":"Liang","year":"2021","journal-title":"Theranostics"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"19","DOI":"10.3389\/fimmu.2015.00019","article-title":"Turning 21: Induction of MiR-21 as a Key Switch in the Inflammatory Response","volume":"6","author":"Sheedy","year":"2015","journal-title":"Front. Immunol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.stem.2013.01.009","article-title":"Modeling Alzheimer\u2019s Disease with IPSCs Reveals Stress Phenotypes Associated with Intracellular A\u03b2 and Differential Drug Responsiveness","volume":"12","author":"Kondo","year":"2013","journal-title":"Cell Stem Cell"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1038\/s41598-018-36993-x","article-title":"Altered Spinogenesis in IPSC-Derived Cortical Neurons from Patients with Autism Carrying de Novo SHANK3 Mutations","volume":"9","author":"Gouder","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1186\/s13195-017-0317-z","article-title":"Neurons Derived from Sporadic Alzheimer\u2019s Disease IPSCs Reveal Elevated TAU Hyperphosphorylation, Increased Amyloid Levels, and GSK3B Activation","volume":"9","author":"Ochalek","year":"2017","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.brainres.2015.11.013","article-title":"Back and Forth in Time: Directing Age in IPSC-Derived Lineages","volume":"1656","author":"Cornacchia","year":"2017","journal-title":"Brain Res."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/s41393-018-0180-1","article-title":"The Protective Effect of MicroRNA-21 in Neurons after Spinal Cord Injury","volume":"57","author":"Zhang","year":"2019","journal-title":"Spin. Cord"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"2522","DOI":"10.3892\/mmr.2017.6862","article-title":"MicroRNA-21 Promotes Neurite Outgrowth by Regulating PDCD4 in a Rat Model of Spinal Cord Injury","volume":"16","author":"Jiang","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1210\/en.2017-03109","article-title":"Functional Roles of Sex-Biased, Growth Hormone\u2013Regulated MicroRNAs MiR-1948 and MiR-802 in Young Adult Mouse Liver","volume":"159","author":"Hao","year":"2018","journal-title":"Endocrinology"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"2430","DOI":"10.1002\/jnr.24075","article-title":"Astrocyte Dysfunction in Alzheimer Disease","volume":"95","author":"Acosta","year":"2017","journal-title":"J. Neurosci. Res."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1002\/glia.23534","article-title":"PPAR\u03b2\/\u03b4-Agonist GW0742 Ameliorates Dysfunction in Fatty Acid Oxidation in PSEN1\u0394E9 Astrocytes","volume":"67","author":"Konttinen","year":"2018","journal-title":"Glia"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"109419","DOI":"10.1016\/j.celrep.2021.109419","article-title":"Tau Oligomer Induced HMGB1 Release Contributes to Cellular Senescence and Neuropathology Linked to Alzheimer\u2019s Disease and Frontotemporal Dementia","volume":"36","author":"Gaikwad","year":"2021","journal-title":"Cell Rep."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"112209","DOI":"10.1016\/j.yexcr.2020.112209","article-title":"Astrocyte Regional Diversity in ALS Includes Distinct Aberrant Phenotypes with Common and Causal Pathological Processes","volume":"395","author":"Gomes","year":"2020","journal-title":"Exp. Cell Res."},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Szpakowski, P., Ksiazek-Winiarek, D., Turniak-Kusy, M., Pacan, I., and Glabinski, A. (2022). Human Primary Astrocytes Differently Respond to Pro- and Anti-Inflammatory Stimuli. Biomedicines, 10.","DOI":"10.3390\/biomedicines10081769"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1007\/s10753-021-01415-0","article-title":"MicroRNA 21 Elicits a Pro-Inflammatory Response in Macrophages, with Exosomes Functioning as Delivery Vehicles","volume":"44","author":"Madhyastha","year":"2021","journal-title":"Inflammation"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1038\/s41593-018-0175-4","article-title":"A 3D Human Triculture System Modeling Neurodegeneration and Neuroinflammation in Alzheimer\u2019s Disease","volume":"21","author":"Park","year":"2018","journal-title":"Nat. Neurosci."},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Adamowicz, M., Kempinska-Podhorodecka, A., Abramczyk, J., Banales, J.M., Milkiewicz, P., and Milkiewicz, M. (2022). Suppression of Hepatic PPAR\u03b1 in Primary Biliary Cholangitis Is Modulated by MiR-155. Cells, 11.","DOI":"10.3390\/cells11182880"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1016\/j.freeradbiomed.2008.09.002","article-title":"PPAR\u03b1 Ligands Inhibit Radiation-Induced Microglial Inflammatory Responses by Negatively Regulating NF-\u039aB and AP-1 Pathways","volume":"45","author":"Ramanan","year":"2008","journal-title":"Free Radic. Biol. Med."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.cmet.2015.05.022","article-title":"HMG-CoA Reductase Inhibitors Bind to PPAR\u03b1 to Upregulate Neurotrophin Expression in the Brain and Improve Memory in Mice","volume":"22","author":"Roy","year":"2015","journal-title":"Cell Metab."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1007\/s11064-020-02993-5","article-title":"The Novel Role of PPAR Alpha in the Brain: Promising Target in Therapy of Alzheimer\u2019s Disease and Other Neurodegenerative Disorders","volume":"45","author":"Strosznajder","year":"2020","journal-title":"Neurochem. Res."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"2631","DOI":"10.1182\/blood-2012-03-415737","article-title":"The Down-Regulation of MiR-125b in Chronic Lymphocytic Leukemias Leads to Metabolic Adaptation of Cells to a Transformed State","volume":"120","author":"Tili","year":"2012","journal-title":"Blood"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1007\/s11064-018-2580-1","article-title":"Knockdown of MicroRNA-21 Promotes Neurological Recovery After Acute Spinal Cord Injury","volume":"48","author":"Xie","year":"2018","journal-title":"Neurochem. Res."},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Chen, C.-H., Hsu, S.-Y., Chiu, C.-C., and Leu, S. (2019). MicroRNA-21 Mediates the Protective Effect of Cardiomyocyte-Derived Conditioned Medium on Ameliorating Myocardial Infarction in Rats. Cells, 8.","DOI":"10.3390\/cells8080935"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.omtn.2020.03.003","article-title":"The Promising Role of MiR-21 as a Cancer Biomarker and Its Importance in RNA-Based Therapeutics","volume":"20","year":"2020","journal-title":"Mol. Ther. Nucleic. Acids"},{"key":"ref_133","first-page":"1434","article-title":"Inhibition of MiR-21 Promotes Cellular Senescence in NT2-Derived Astrocytes","volume":"86","author":"Balint","year":"2021","journal-title":"Biochemistry"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"10859","DOI":"10.1096\/fj.201900743R","article-title":"Silencing MiR-21 Induces Polarization of Astrocytes to the A2 Phenotype and Improves the Formation of Synapses by Targeting Glypican 6 via the Signal Transducer and Activator of Transcription-3 Pathway after Acute Ischemic Spinal Cord Injury","volume":"33","author":"Su","year":"2019","journal-title":"FASEB J."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.18632\/aging.101484","article-title":"MicroRNA-21 Regulates Astrocytic Reaction Post-Acute Phase of Spinal Cord Injury through Modulating TGF-\u03b2 Signaling","volume":"10","author":"Liu","year":"2018","journal-title":"Aging"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"jcs239004","DOI":"10.1242\/jcs.239004","article-title":"Schwann Cell Reprogramming into Repair Cells Increases MiRNA-21 Expression in Exosomes Promoting Axonal Growth","volume":"133","author":"Saquel","year":"2020","journal-title":"J. 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