Evidence map›Paper›PMID 34057756›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2022

Mitochondrial ROS control neuronal excitability and cell fate in frontotemporal dementia.

Noemí Esteras, Olga Kopach, Marta Maiolino, Vincenzo Lariccia, Salvatore Amoroso, Seema Qamar, Selina Wray, Dmitri A Rusakov, Morana Jaganjac, Andrey Y Abramov

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
5.6field-weighted citation impact, top 3% 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

45 citing papers in PubMed, 60 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Review
  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

10 authors at 4 institutions in 5 countries.

Noemí EsterasDepartment of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK.ORCID 0000-0002-7938-6131
Olga KopachDepartment of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, UK.
Marta MaiolinoDepartment of Biomedical Sciences and Public Health, School of Medicine, University "Politecnica delle Marche,", Ancona, Italy.
Vincenzo LaricciaDepartment of Biomedical Sciences and Public Health, School of Medicine, University "Politecnica delle Marche,", Ancona, Italy.
Salvatore AmorosoDepartment of Biomedical Sciences and Public Health, School of Medicine, University "Politecnica delle Marche,", Ancona, Italy.
Seema QamarDepartment of Clinical Neurosciences, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
Selina WrayDepartment of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK.
Dmitri A RusakovDepartment of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, UK.
Morana JaganjacQatar Analytics & BioResearch Lab, Anti-Doping Lab Qatar, Doha, Qatar.
Andrey Y AbramovDepartment of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK.
National Hospital for Neurology and Neurosurgery · GBMarche Polytechnic University · ITRuđer Bošković Institute · HRUniversity of Cambridge · GB

Funding

Department of HealthWellcome Trust
6 · The paper itself

Abstract

introductionThe second most common form of early-onset dementia-frontotemporal dementia (FTD)-is often characterized by the aggregation of the microtubule-associated protein tau. Here we studied the mechanism of tau-induced neuronal dysfunction in neurons with the FTD-related 10+16 MAPT mutation.

methodsLive imaging, electrophysiology, and redox proteomics were used in 10+16 induced pluripotent stem cell-derived neurons and a model of tau spreading in primary cultures.

resultsOverproduction of mitochondrial reactive oxygen species (ROS) in 10+16 neurons alters the trafficking of specific glutamate receptor subunits via redox regulation. Increased surface expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors containing GluA1 and NR2B subunits leads to impaired glutamatergic signaling, calcium overload, and excitotoxicity. Mitochondrial antioxidants restore the altered response and prevent neuronal death. Importantly, extracellular 4R tau induces the same pathological response in healthy neurons, thus proposing a mechanism for disease propagation. DISCUSSION: These results demonstrate mitochondrial ROS modulate glutamatergic signaling in FTD, and suggest a new therapeutic strategy.

Indexed as

Frontotemporal DementiaInduced Pluripotent Stem CellsHumansMitochondriaNeuronsReactive Oxygen SpeciesReceptors, N-Methyl-D-Aspartatetau ProteinsReactive Oxygen SpeciesReceptors, N-Methyl-D-Aspartatetau Proteins4R tauAMPA receptorscalcium signalingfrontotemporal dementiaglutamateinduced pluripotent stem cellsMAPT 10+16mitochondrial antioxidantsmitochondrial reactive oxygen speciesNMDA receptorstau

Identifiers

PMID34057756
PMCPMC12086756
OpenAlexW3165842025

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.