Neuronal Dynamics and miRNA Signaling Differ between SH-SY5Y
| Autor: | Gonçalo, Garcia, Sara, Pinto, Mar, Cunha, Adelaide, Fernandes, Jari, Koistinaho, Dora, Brites |
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| Rok vydání: | 2021 |
| Předmět: |
Neurons
neuropathological hallmarks of AD cell experimental models inflammatory-associated miRNAs Induced Pluripotent Stem Cells Alzheimer’s disease (AD) neuronal dysfunction miR-124-3p modulation Exosomes paracrine signaling Article iPSC-derived neurons Amyloid beta-Protein Precursor MicroRNAs Neuroblastoma secretome Alzheimer Disease Mutation Presenilin-1 Humans Signal Transduction small extracellular vesicles (exosomes) |
| Zdroj: | Cells |
| ISSN: | 2073-4409 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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