Evidence map›Paper›PMID 34200161›Full record

ArticleInternational journal of molecular sciences2021

Overexpression of miR-124 in Motor Neurons Plays a Key Role in ALS Pathological Processes.

Ana Rita Vaz, Daniela Vizinha, Hermes Morais, Ana Rita Colaço, Gecioni Loch-Neckel, Marta Barbosa, Dora Brites

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed, 1 pooled it
3.6field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

34 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Review
  5. Review
  6. Article
  7. Review
  8. Article
  9. Review
  10. Review
  11. Article
  12. Article
  13. Review
  14. Article
  15. Review
  16. Article
  17. Review
  18. Article
  19. Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Ana Rita VazNeuroinflammation, Signaling and Neuroregeneration Group, Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal.ORCID 0000-0002-3418-3269
Daniela VizinhaNeuroinflammation, Signaling and Neuroregeneration Group, Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal.
Hermes MoraisNeuroinflammation, Signaling and Neuroregeneration Group, Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal.
Ana Rita ColaçoNeuroinflammation, Signaling and Neuroregeneration Group, Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal.
Gecioni Loch-NeckelNeuroinflammation, Signaling and Neuroregeneration Group, Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal.
Marta BarbosaNeuroinflammation, Signaling and Neuroregeneration Group, Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal.ORCID 0000-0003-1735-3251
Dora BritesNeuroinflammation, Signaling and Neuroregeneration Group, Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal.ORCID 0000-0002-3024-9777
University of Lisbon · PT

Funding

Fundação para a Ciência e a Tecnologia PTDC/MED-NEU/31395/2017Fundação para a Ciência e a Tecnologia SFRH/BD/129586/2017Fundação para a Ciência e a Tecnologia UIDB/04138/2020Fundação para a Ciência e a Tecnologia UIDP/04138/2020Programa Operacional Competitividade e Internacionalização FEDER-031395Programa Operacional Regional de Lisboa LISBOA- 01-0145Santa Casa da Misericórdia de Lisboa ELA-2015-002
6 · The paper itself

Abstract

miRNA(miR)-124 is an important regulator of neurogenesis, but its upregulation in SOD1G93A motor neurons (mSOD1 MNs) was shown to associate with neurodegeneration and microglia activation. We used pre-miR-124 in wild-type (WT) MNs and anti-miR-124 in mSOD1 MNs to characterize the miR-124 pathological role. miR-124 overexpression in WT MNs produced a miRNA profile like that of mSOD1 MNs (high miR-125b; low miR-146a and miR-21), and similarly led to early apoptosis. Alterations in mSOD1 MNs were abrogated with anti-miR-124 and changes in their miRNAs mostly recapitulated by their secretome. Normalization of miR-124 levels in mSOD1 MNs prevented the dysregulation of neurite network, mitochondria dynamics, axonal transport, and synaptic signaling. Same alterations were observed in WT MNs after pre-miR-124 transfection. Secretome from mSOD1 MNs triggered spinal microglia activation, which was unno-ticed with that from anti-miR-124-modulated cells. Secretome from such modulated MNs, when added to SC organotypic cultures from mSOD1 mice in the early symptomatic stage, also coun-teracted the pathology associated to GFAP decrease, PSD-95 and CX3CL1-CX3CR1 signaling im-pairment, neuro-immune homeostatic imbalance, and enhanced miR-124 expression levels. Data suggest that miR-124 is implicated in MN degeneration and paracrine-mediated pathogenicity. We propose miR-124 as a new therapeutic target and a promising ALS biomarker in patient sub-populations.

Indexed as

Disease Models, AnimalAmyotrophic Lateral SclerosisAnimalsBiomarkersFemaleHumansMaleMiceMice, Inbred C57BLMice, TransgenicMicroRNAsMitochondriaMotor NeuronsSignal TransductionSuperoxide Dismutase-1BiomarkersMicroRNAsMirn124 microRNA, mouseSOD1 protein, humanSuperoxide Dismutase-1amyotrophic lateral sclerosisinflamma-miRNAsmiR-124 modulationmotor neuron regenerationmotor neuron secretomemSOD1 mice modelneuro-immune deregulationparacrine signaling regulationspinal microgliaspinal organotypic cultures

Identifiers

PMID34200161
PMCPMC8201298
OpenAlexW3167762194

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.