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Cited by 39Alzheimer's disease research and treatmentsMicroRNA in disease regulationNeuroinflammation and Neurodegeneration Mechanisms

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, Gonçalo, Pinto, Sara, Cunha, Mar, Fernandes, Adelaide, Koistinaho, Jari, Brites, Dora·2021·Cells
DOI 10.3390/cells10092424PMC PMC8465877
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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 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.

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Authors
Garcia, G., Pinto, S., Cunha, M., Fernandes, A., Koistinaho, J., & Brites, D.
Affiliations
  • University of Lisbon (PT)
  • A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, FI-70211 Kuopio, Finland
Corresponding author
Brites, Dora
ORCID
Venue
Cells
Publisher
MDPI AG
Published
2021-09-14
Volume
10
Issue
9
Pages
2424
ISSN
2073-4409 (ISSN-L)
DOI
10.3390/cells10092424
PMC
PMC8465877
OpenAlex
W3199745811
Cited by
39
References
10
Citations by year
2026: 7 · 2025: 9 · 2024: 7 · 2023: 9 · 2022: 7
FWCI
3.61
Type
journal article
Language
en
Open access
Licence
Locations
  • Cells (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Työväentutkimus Vuosikirja (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, other-oa)
Funders
Fundação para a Ciência e a Tecnologia (JPco-fuND/0003/2015, PTDC/MED-NEU/31395/2017)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
Alzheimer's disease, miR-124, microRNA dysregulation, iPSC-derived neurons, PSEN1 mutations, APPswe, exosomes, miR-125b, miR-21, miR-146a, miR-155, amyloid-beta oligomers, tau phosphorylation, neurite outgrowth, dendritic spine density, mitochondrial activation, neuron models
MeSH terms
Alzheimer Disease, Humans, Mutation, Neuroblastoma, Neurons, Signal Transduction, Amyloid beta-Protein Precursor, MicroRNAs, Presenilin-1, Exosomes, Induced Pluripotent Stem Cells

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