Evidence map›Paper›PMID 34741697›Full record

ArticleCellular and molecular neurobiology2023

Loss of SORCS2 is Associated with Neuronal DNA Double-Strand Breaks.

Katerina O Gospodinova, Ditte Olsen, Mathias Kaas, Susan M Anderson, Jonathan Phillips, Rosie M Walker, Mairead L Bermingham, Abigail L Payne, Panagiotis Giannopoulos, Divya Pandya and 5 more

Open access · hybridAbstract read
In one paragraph

Article in Cellular and molecular neurobiology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
0.4field-weighted citation impact, top 40% 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

6 citing papers in PubMed, 1 synthesis or guideline pooled it, 7 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Article
  6. 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

15 authors at 3 institutions in 2 countries.

Katerina O GospodinovaCentre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, EH4 2XU, UK.
Ditte OlsenDepartment of Biomedicine, Aarhus University, 8000, Aarhus, Denmark.
Mathias KaasDepartment of Biomedicine, Aarhus University, 8000, Aarhus, Denmark.
Susan M AndersonCentre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, EH4 2XU, UK.
Jonathan PhillipsCentre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, EH4 2XU, UK.
Rosie M WalkerCentre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, EH4 2XU, UK.
Mairead L BerminghamCentre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, EH4 2XU, UK.
Abigail L PayneCentre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, EH4 2XU, UK.
Panagiotis GiannopoulosCentre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, EH4 2XU, UK.
Divya PandyaCentre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, EH4 2XU, UK.
Tara L Spires-JonesCentre for Discovery Brain Sciences, UK Dementia Research Institute, University of Edinburgh, Edinburgh, EH8 9XD, UK.
Catherine M AbbottCentre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, EH4 2XU, UK.
David J PorteousCentre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, EH4 2XU, UK.
Simon GlerupDepartment of Biomedicine, Aarhus University, 8000, Aarhus, Denmark.
Kathryn L EvansCentre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, EH4 2XU, UK. Kathy.Evans@ed.ac.uk.ORCID http://orcid.org/0000-0002-7884-5877
Edinburgh Cancer Research · GBAarhus University · DKUK Dementia Research Institute · GB

Funding

Alzheimer's Research UK ARUK-NC2019-SCO
6 · The paper itself

Abstract

SORCS2 is one of five proteins that constitute the Vps10p-domain receptor family. Members of this family play important roles in cellular processes linked to neuronal survival, differentiation and function. Genetic and functional studies implicate SORCS2 in cognitive function, as well as in neurodegenerative and psychiatric disorders. DNA damage and DNA repair deficits are linked to ageing and neurodegeneration, and transient neuronal DNA double-strand breaks (DSBs) also occur as a result of neuronal activity. Here, we report a novel role for SORCS2 in DSB formation. We show that SorCS2 loss is associated with elevated DSB levels in the mouse dentate gyrus and that knocking out SORCS2 in a human neuronal cell line increased Topoisomerase IIβ-dependent DSB formation and reduced neuronal viability. Neuronal stimulation had no impact on levels of DNA breaks in vitro, suggesting that the observed differences may not be the result of aberrant neuronal activity in these cells. Our findings are consistent with studies linking the VPS10 receptors and DNA damage to neurodegenerative conditions.

Indexed as

DNA Breaks, Double-StrandedDNA RepairAnimalsCell LineDNA DamageHumansMiceNerve Tissue ProteinsNeuronsReceptors, Cell SurfaceNerve Tissue ProteinsReceptors, Cell SurfaceSORCS2 protein, humanSorCS2 protein, mouseDNA double-strand breaksNeurodegenerationNeuronal activitySORCS2

Identifiers

PMID34741697
PMCPMC9813074
OpenAlexW3212453134

What OpenQuestion holds

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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.