Evidence map›Paper›PMID 31401765›Full record

ArticleMolecular neurobiology2020

Calpain Activation Is the Major Cause of Cell Death in Photoreceptors Expressing a Rhodopsin Misfolding Mutation.

Antonella Comitato, Davide Schiroli, Monica Montanari, Valeria Marigo

Open access · greenAbstract read
PubMed Publisher
In one paragraph

Article in Molecular neurobiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

25 citing papers in PubMed, 31 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. Review
  9. Bridging the gap of vision restoration.Frontiers in cellular neuroscience · 2024
    Review
  10. cGMP Signaling in Photoreceptor Degeneration.International journal of molecular sciences · 2023
    Review
  11. Review
  12. GADD34 Ablation Exacerbates Retinal Degeneration in P23H RHO Mice.International journal of molecular sciences · 2022
    Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Review
  19. New In Vitro Cellular Model for Molecular Studies of Retinitis Pigmentosa.International journal of molecular sciences · 2021
    Article
  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

4 authors at 1 institution in 1 country.

Antonella ComitatoDepartment of Life Sciences, University of Modena and Reggio Emilia, via Campi, 287, 41125, Modena, Italy.
Davide SchiroliDepartment of Life Sciences, University of Modena and Reggio Emilia, via Campi, 287, 41125, Modena, Italy.
Monica MontanariDepartment of Life Sciences, University of Modena and Reggio Emilia, via Campi, 287, 41125, Modena, Italy.
Valeria MarigoDepartment of Life Sciences, University of Modena and Reggio Emilia, via Campi, 287, 41125, Modena, Italy. valeria.marigo@unimore.it.ORCID http://orcid.org/0000-0002-4428-2084
University of Modena and Reggio Emilia · IT

Funding

Fondazione Roma call for proposals 2013 on Retinitis PigmentosaFondazione Telethon GGP11210, GGP14180H2020 transMed, MSCA-ITN-2017-765441
6 · The paper itself

Abstract

The majority of mutations in rhodopsin (RHO) cause misfolding of the protein and has been linked to degeneration of photoreceptor cells in the retina. A lot of attention has been set on targeting ER stress for the development of new therapies for inherited retinal degeneration caused by mutations in the RHO gene. Nevertheless, the cell death pathway activated by RHO misfolded protein is still debated. In this study, we analyzed the retina of the knock-in mouse expressing the P23H misfolded mutant RHO. We found persistent unfolded protein response (UPR) during degeneration. Interestingly, long-term stimulation of the PERK branch of ER stress had a protective effect by phosphorylating nuclear factor erythroid 2-related factor 2 (NRF2) transcription factor, associated with antioxidant responses. Otherwise, we provide evidence that increased intracellular calcium and activation of calpains strongly correlated with rod photoreceptor cell death. By blocking calpain activity, we significantly decreased the activation of caspase-7 and apoptosis-inducing factor (AIF), two cell death effectors, and cell demise, and effectively protected the retina from degeneration caused by the P23H dominant mutation in RHO.

Indexed as

ApoptosisProtein FoldingAnimalsCalciumCalpaineIF-2 KinaseEndoplasmic Reticulum StressEnzyme ActivationIntracellular SpaceMice, Inbred C57BLMutationPhotoreceptor Cells, VertebrateProtein Kinase InhibitorsRetinal DegenerationRhodopsinUnfolded Protein ResponseCalciumCalpaineIF-2 KinaseProtein Kinase InhibitorsRhodopsinadRPeIF2αGSK2606414APD150606RodSpectrinZ-VAD-FMK

Identifiers

PMID31401765
OpenAlexW2968314941

What OpenQuestion holds

Textmetadata
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.