Evidence map›Paper›PMID 27845394›Full record

ArticleScientific reports2016

Calpain-mediated cleavage of collapsin response mediator protein-2 drives acute axonal degeneration.

Jian-Nan Zhang, Uwe Michel, Christof Lenz, Caroline C Friedel, Sarah Köster, Zara d'Hedouville, Lars Tönges, Henning Urlaub, Mathias Bähr, Paul Lingor and 1 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2016. 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
2.7field-weighted citation impact, top 10% 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, 59 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Review
  18. Article
  19. 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

11 authors at 4 institutions in 1 country.

Jian-Nan ZhangDepartment of Neurology, University Medicine Göttingen, 37075 Göttingen, Germany.
Uwe MichelDepartment of Neurology, University Medicine Göttingen, 37075 Göttingen, Germany.
Christof LenzBioanalytical Mass Spectrometry, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany.
Caroline C FriedelInstitute for Informatics, LMU Munich, 80333 Munich, Germany.
Sarah KösterInstitute for X-Ray Physics, Georg-August-University Göttingen, 37077 Göttingen, Germany.
Zara d'HedouvilleDepartment of Neurology, University Medicine Göttingen, 37075 Göttingen, Germany.
Lars TöngesDepartment of Neurology, University Medicine Göttingen, 37075 Göttingen, Germany.
Henning UrlaubBioanalytical Mass Spectrometry, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany.
Mathias BährDepartment of Neurology, University Medicine Göttingen, 37075 Göttingen, Germany.
Paul LingorDepartment of Neurology, University Medicine Göttingen, 37075 Göttingen, Germany.
Jan C KochDepartment of Neurology, University Medicine Göttingen, 37075 Göttingen, Germany.
Universitätsmedizin Göttingen · DENanoscale Microscopy and Molecular Physiology of the Brain Cluster of Excellence 171 — DFG Research Center 103 · DEMax Planck Institute for Biophysical Chemistry · DELudwig-Maximilians-Universität München · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Axonal degeneration is a key initiating event in many neurological diseases. Focal lesions to axons result in a rapid disintegration of the perilesional axon by acute axonal degeneration (AAD) within several hours. However, the underlying molecular mechanisms of AAD are only incompletely understood. Here, we studied AAD in vivo through live-imaging of the rat optic nerve and in vitro in primary rat cortical neurons in microfluidic chambers. We found that calpain is activated early during AAD of the optic nerve and that calpain inhibition completely inhibits axonal fragmentation on the proximal side of the crush while it attenuates AAD on the distal side. A screening of calpain targets revealed that collapsin response mediator protein-2 (CRMP2) is a main downstream target of calpain activation in AAD. CRMP2-overexpression delayed bulb formation and rescued impairment of axonal mitochondrial transport after axotomy in vitro. In vivo, CRMP2-overexpression effectively protected the proximal axon from fragmentation within 6 hours after crush. Finally, a proteomic analysis of the optic nerve was performed at 6 hours after crush, which identified further proteins regulated during AAD, including several interactors of CRMP2. These findings reveal CRMP2 as an important mediator of AAD and define it as a putative therapeutic target.

Indexed as

Acute DiseaseAnimalsAxonsCalpainCells, CulturedIntercellular Signaling Peptides and ProteinsNerve DegenerationNerve Tissue ProteinsOptic Nerve DiseasesRatsCalpaincollapsin response mediator protein-2Intercellular Signaling Peptides and ProteinsNerve Tissue Proteins

Identifiers

PMID27845394
PMCPMC5109185
OpenAlexW2552491411

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.