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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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

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
Author: Garcia, Goncalo; Pinto, Sara; Cunha, Mar; Fernandes, Adelaide; Koistinaho, Jari; Brites, Dora
Contributor: University of Helsinki, Neuroscience Center
Date: 2021-09
Language: eng
Number of pages: 27
Belongs to series: Cells
ISSN: 2073-4409
URI: http://hdl.handle.net/10138/335751
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.
Subject: Alzheimer's disease (AD)
cell experimental models
inflammatory-associated miRNAs
iPSC-derived neurons
miR-124-3p modulation
neuronal dysfunction
neuropathological hallmarks of AD
paracrine signaling
secretome
small extracellular vesicles (exosomes)
ALZHEIMERS-DISEASE
NEURITE OUTGROWTH
TAU-PROTEIN
CELLS
DIFFERENTIATION
MICRORNAS
HYPERPHOSPHORYLATION
TRANSFECTION
EXPRESSION
APOPTOSIS
3112 Neurosciences
1182 Biochemistry, cell and molecular biology
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