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
| Autor: | Gonçalo Garcia, Adelaide Fernandes, Sara Pinto, Dora Brites, Mar Cunha, Jari Koistinaho |
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| Přispěvatelé: | Repositório da Universidade de Lisboa, Neuroscience Center, Helsinki Institute of Life Science HiLIFE |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
EXPRESSION
SH-SY5Y Neurite MICRORNAS QH301-705.5 Tau protein Alzheimer’s disease (AD) HYPERPHOSPHORYLATION miR-124-3p modulation NEURITE OUTGROWTH iPSC-derived neurons TRANSFECTION 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Amyloid precursor protein Biology (General) Neuropathological hallmarks of AD 030304 developmental biology Secretome Paracrine signaling TAU-PROTEIN 0303 health sciences biology 3112 Neurosciences Neuronal dysfunction General Medicine Transfection Microvesicles APOPTOSIS 3. Good health Cell biology ALZHEIMERS-DISEASE Cell experimental models DIFFERENTIATION Inflammatory-associated miRNAs Alzheimer's disease (AD) CELLS biology.protein 1182 Biochemistry cell and molecular biology Cellular model Small extracellular vesicles (exosomes) Alzheimer’s disease 030217 neurology & neurosurgery |
| Zdroj: | Repositório Científico de Acesso Aberto de Portugal Repositório Científico de Acesso Aberto de Portugal (RCAAP) instacron:RCAAP Cells Volume 10 Issue 9 Cells, Vol 10, Iss 2424, p 2424 (2021) |
| Popis: | © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). 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 Aβ 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. This work is part of an EU Joint Program—Neurodegenerative Disease Research (JPND) project—supported by Fundação para a Ciência e a Tecnologia (FCT) (JPco-fuND/0003/2015 and PTDC/MED-NEU/31395/2017 to Dora Brites, UID/DTP/04138/2019 and UIDB/UIDP/04138/2020 to iMed.ULisboa, and PhD fellowship SFRH/BD/128738/2017 to Gonçalo Garcia). |
| Databáze: | OpenAIRE |
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