Evidence map›Paper›PMID 26209654›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2015

Local axonal protection by WldS as revealed by conditional regulation of protein stability.

Jack T Wang, Zachary A Medress, Mauricio E Vargas, Ben A Barres

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

Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
1.8field-weighted citation impact, top 16% 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

33 citing papers in PubMed, 48 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Jack T WangDepartment of Neurobiology, Stanford University School of Medicine, Stanford, CA 94305; jtw@alumni.stanford.edu barres@stanford.edu.
Zachary A MedressDepartment of Neurobiology, Stanford University School of Medicine, Stanford, CA 94305;
Mauricio E VargasDepartment of Ophthalmology, Jules Stein Eye Institute, University of California, Los Angeles, CA 90095.
Ben A BarresDepartment of Neurobiology, Stanford University School of Medicine, Stanford, CA 94305; jtw@alumni.stanford.edu barres@stanford.edu.
Stanford University · USUniversity of California, Los Angeles · US

Funding

RANDOMIZED TRIAL FOR RETINITIS PIGMENTOSAU10EY011030 · NEI · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI BERSON, ELIOT L · 1995 to 2001
$1.6M
Howard Hughes Medical InstituteNEI NIH HHS R01 EY11030
6 · The paper itself

Abstract

The expression of the mutant Wallerian degeneration slow (WldS) protein significantly delays axonal degeneration from various nerve injuries and in multiple species; however, the mechanism for its axonal protective property remains unclear. Although WldS is localized predominantly in the nucleus, it also is present in a smaller axonal pool, leading to conflicting models to account for the WldS fraction necessary for axonal protection. To identify where WldS activity is required to delay axonal degeneration, we adopted a method to alter the temporal expression of WldS protein in neurons by chemically regulating its protein stability. We demonstrate that continuous WldS activity in the axonal compartment is both necessary and sufficient to delay axonal degeneration. Furthermore, by specifically increasing axonal WldS expression postaxotomy, we reveal a critical period of 4-5 h postinjury during which the course of Wallerian axonal degeneration can be halted. Finally, we show that NAD(+), the metabolite of WldS/nicotinamide mononucleotide adenylyltransferase enzymatic activity, is sufficient and specific to confer WldS-like axon protection and is a likely molecular mediator of WldS axon protection. The results delineate a therapeutic window in which the course of Wallerian degeneration can be delayed even after injures have occurred and help narrow the molecular targets of WldS activity to events within the axonal compartment.

Indexed as

Gene Expression RegulationAnimalsAxonsCytoplasmDisease ProgressionGene Expression ProfilingHEK293 CellsHumansLigandsMiceMice, Inbred C57BLMicroscopy, FluorescenceModels, NeurologicalNADPNerve Tissue ProteinsNervous System DiseasesLigandsNADPNerve Tissue ProteinsWld protein, rataxon degenerationaxotomyNAD+Wallerian degenerationWldS

Identifiers

PMID26209654
PMCPMC4547231
OpenAlexW2117108791

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.