Evidence map›Paper›PMID 18820287›Full record

ArticleCerebral cortex (New York, N.Y. : 1991)2009

Molecular regulation of DNA damage-induced apoptosis in neurons of cerebral cortex.

Lee J Martin, Zhiping Liu, Jacqueline Pipino, Barry Chestnut, Melissa A Landek

Open access · bronzeAbstract read
In one paragraph

Article in Cerebral cortex (New York, N.Y. : 1991), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed, 1 pooled it
2.9field-weighted citation impact, top 9% 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

43 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. DNA damage and repair: underlying mechanisms leading to microcephaly.Frontiers in cell and developmental biology · 2023
    Review
  5. Review
  6. Roles for c-Abl in postoperative neurodegeneration.International journal of medical sciences · 2022
    Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
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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

5 authors at 2 institutions in 2 countries.

Lee J MartinDepartment of Pathology, Division of Neuropathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA. martinl@jhmi.edu
Zhiping Liu
Jacqueline Pipino
Barry Chestnut
Melissa A Landek
Institute of Neuroimmunology of the Slovak Academy of Sciences · SKJohns Hopkins Medicine · US

Funding

MECHANISMS OF NEURONAL APOPTOSIS IN VIVOR01AG016282 · NIA · JOHNS HOPKINS UNIVERSITY · PI MARTIN, LEE J · 2000 to 2009
$2.6M
MOTOR NEURON DEATH AND GLUTAMATE RECEPTORSR01NS034100 · NINDS · JOHNS HOPKINS UNIVERSITY · PI MARTIN, LEE J · 1996 to 2006
$2.1M
DNA Damage/Repair and Cell DeathR01NS052098 · NINDS · JOHNS HOPKINS UNIVERSITY · PI MARTIN, LEE J · 2005 to 2009
$1.5M
NIA NIH HHS AG016282NIA NIH HHS R01 AG016282NINDS NIH HHS NS034100NINDS NIH HHS NS052098
6 · The paper itself

Abstract

Cerebral cortical neuron degeneration occurs in brain disorders manifesting throughout life, but the mechanisms are understood poorly. We used cultured embryonic mouse cortical neurons and an in vivo mouse model to study mechanisms of DNA damaged-induced apoptosis in immature and differentiated neurons. p53 drives apoptosis of immature and differentiated cortical neurons through its rapid and prominent activation stimulated by DNA strand breaks induced by topoisomerase-I and -II inhibition. Blocking p53-DNA transactivation with alpha-pifithrin protects immature neurons; blocking p53-mitochondrial functions with mu-pifithrin protects differentiated neurons. Mitochondrial death proteins are upregulated in apoptotic immature and differentiated neurons and have nonredundant proapoptotic functions; Bak is more dominant than Bax in differentiated neurons. p53 phosphorylation is mediated by ataxia telangiectasia mutated (ATM) kinase. ATM inactivation is antiapoptotic, particularly in differentiated neurons, whereas inhibition of c-Abl protects immature neurons but not differentiated neurons. Cell death protein expression patterns in mouse forebrain are mostly similar to cultured neurons. DNA damage induces prominent p53 activation and apoptosis in cerebral cortex in vivo. Thus, DNA strand breaks in cortical neurons induce rapid p53-mediated apoptosis through actions of upstream ATM and c-Abl kinases and downstream mitochondrial death proteins. This molecular network operates through variations depending on neuron maturity.

Indexed as

AnimalsApoptosisApoptosis Regulatory ProteinsCells, CulturedCerebral CortexDNA DamageMiceNeuronsTumor Suppressor Protein p53Apoptosis Regulatory ProteinsTumor Suppressor Protein p53

Identifiers

PMID18820287
PMCPMC2677647
OpenAlexW2143072030

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.