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

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dc.contributor.author Garcia, Goncalo
dc.contributor.author Pinto, Sara
dc.contributor.author Cunha, Mar
dc.contributor.author Fernandes, Adelaide
dc.contributor.author Koistinaho, Jari
dc.contributor.author Brites, Dora
dc.date.accessioned 2021-10-27T14:40:01Z
dc.date.available 2021-10-27T14:40:01Z
dc.date.issued 2021-09
dc.identifier.citation Garcia , G , Pinto , S , Cunha , M , Fernandes , A , Koistinaho , J & 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 , vol. 10 , no. 9 , 2424 . https://doi.org/10.3390/cells10092424
dc.identifier.other PURE: 169826554
dc.identifier.other PURE UUID: e700d006-939e-43a1-ab3d-86f4c1764afc
dc.identifier.other WOS: 000699190500001
dc.identifier.other ORCID: /0000-0001-6559-1153/work/102175483
dc.identifier.uri http://hdl.handle.net/10138/335751
dc.description.abstract Neuronal miRNA dysregulation may have a role in the pathophysiology of Alzheimer's disease (AD). miRNA(miR)-124 is largely abundant and a critical player in many neuronal functions. However, the lack of models reliably recapitulating AD pathophysiology hampers our understanding of miR-124's role in the disease. Using the classical human SH-SY5Y-APP695 Swedish neuroblastoma cells (SH-SWE) and the PSEN1 mutant iPSC-derived neurons (iNEU-PSEN), we observed a sustained upregulation of miR-124/miR-125b/miR-21, but only miR-124 was consistently shuttled into their exosomes. The miR-124 mimic reduced APP gene expression in both AD models. While miR-124 mimic in SH-SWE neurons led to neurite outgrowth, mitochondria activation and small A beta oligomer reduction, in iNEU-PSEN cells it diminished Tau phosphorylation, whereas miR-124 inhibitor decreased dendritic spine density. In exosomes, cellular transfection with the mimic predominantly downregulated miR-125b/miR-21/miR-146a/miR-155. The miR-124 inhibitor upregulated miR-146a in the two experimental cell models, while it led to distinct miRNA signatures in cells and exosomes. In sum, though miR-124 function may be dependent on the neuronal AD model, data indicate that keeping miR-124 level strictly controlled is crucial for proper neuronal function. Moreover, the iNEU-PSEN cellular model stands out as a useful tool for AD mechanistic studies and perhaps for the development of personalized therapeutic strategies. en
dc.format.extent 27
dc.language.iso eng
dc.relation.ispartof Cells
dc.rights cc_by
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject Alzheimer's disease (AD)
dc.subject cell experimental models
dc.subject inflammatory-associated miRNAs
dc.subject iPSC-derived neurons
dc.subject miR-124-3p modulation
dc.subject neuronal dysfunction
dc.subject neuropathological hallmarks of AD
dc.subject paracrine signaling
dc.subject secretome
dc.subject small extracellular vesicles (exosomes)
dc.subject ALZHEIMERS-DISEASE
dc.subject NEURITE OUTGROWTH
dc.subject TAU-PROTEIN
dc.subject CELLS
dc.subject DIFFERENTIATION
dc.subject MICRORNAS
dc.subject HYPERPHOSPHORYLATION
dc.subject TRANSFECTION
dc.subject EXPRESSION
dc.subject APOPTOSIS
dc.subject 3112 Neurosciences
dc.subject 1182 Biochemistry, cell and molecular biology
dc.title 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 en
dc.type Article
dc.contributor.organization Neuroscience Center
dc.contributor.organization Helsinki Institute of Life Science HiLIFE
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.3390/cells10092424
dc.relation.issn 2073-4409
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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