Evidence map›Paper›PMID 31725979›Full record

ArticleAnnals of clinical and translational neurology2019

A CXCR4 receptor agonist strongly stimulates axonal regeneration after damage.

Giulia Zanetti, Samuele Negro, Aram Megighian, Andrea Mattarei, Florigio Lista, Silvia Fillo, Michela Rigoni, Marco Pirazzini, Cesare Montecucco

Open access · goldAbstract read
In one paragraph

Article in Annals of clinical and translational neurology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.1field-weighted citation impact, top 20% 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

18 citing papers in PubMed, 31 citations in OpenAlex.

  1. Article
  2. Probing the properties of PTEN specific botulinum toxin type E mutants.Journal of neural transmission (Vienna, Austria : 1996) · 2025
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  15. Neurotransmission Recovery by Melatonin Measured by CMAP.Methods in molecular biology (Clifton, N.J.) · 2022
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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

9 authors at 1 institution in 1 country.

Giulia ZanettiDepartment of Biomedical Sciences, University of Padua, Padua, Italy.ORCID 0000-0001-9350-1047
Samuele NegroDepartment of Biomedical Sciences, University of Padua, Padua, Italy.
Aram MegighianDepartment of Biomedical Sciences, University of Padua, Padua, Italy.
Andrea MattareiDepartment of Pharmaceutical and Pharmacological Sciences, University of Padua, Padua, Italy.
Florigio ListaScientific Department, Army Medical Center, Roma, Italy.
Silvia FilloScientific Department, Army Medical Center, Roma, Italy.
Michela RigoniDepartment of Biomedical Sciences, University of Padua, Padua, Italy.
Marco PirazziniDepartment of Biomedical Sciences, University of Padua, Padua, Italy.ORCID 0000-0003-4127-254X
Cesare MontecuccoDepartment of Biomedical Sciences, University of Padua, Padua, Italy.ORCID 0000-0001-7361-5688
University of Padua · IT

Funding

Ministero della DifesaUniversity of Padua
6 · The paper itself

Abstract

objectiveTo test whether the signaling axis CXCL12α-CXCR4 is activated upon crush/cut of the sciatic nerve and to test the activity of NUCC-390, a new CXCR4 agonist, in promoting nerve recovery from damage.

methodsThe sciatic nerve was either crushed or cut. Expression and localization of CXCL12α and CXCR4 were evaluated by imaging with specific antibodies. Their functional involvement in nerve regeneration was determined by antibody-neutralization of CXCL12α, and by the CXCR4 specific antagonist AMD3100, using as quantitative read-out the compound muscle action potential (CMAP). NUCC-390 activity on nerve regeneration was determined by imaging and CMAP recordings.

resultsCXCR4 is expressed at the injury site within the axonal compartment, whilst its ligand CXCL12α is expressed in Schwann cells. The CXCL12α-CXCR4 axis is involved in the recovery of neurotransmission of the injured nerve. More importantly, the small molecule NUCC-390 is a strong promoter of the functional and anatomical recovery of the nerve, by acting very similarly to CXCL12α. This pharmacological action is due to the capability of NUCC-390 to foster elongation of motor neuron axons both in vitro and in vivo.

interpretationImaging and electrophysiological data provide novel and compelling evidence that the CXCL12α-CXCR4 axis is involved in sciatic nerve repair after crush/cut. This makes NUCC-390 a strong candidate molecule to stimulate nerve repair by promoting axonal elongation. We propose this molecule to be tested in other models of neuronal damage, to lay the basis for clinical trials on the efficacy of NUCC-390 in peripheral nerve repair in humans.

Indexed as

AnimalsAxonsBenzylaminesChemokine CXCL12CyclamsDisease Models, AnimalHeterocyclic CompoundsIndazolesMiceMice, Inbred C57BLNerve RegenerationPiperidinesPyridinesReceptors, CXCR4Schwann CellsSciatic NerveBenzylaminesChemokine CXCL12Cxcl12 protein, mouseCXCR4 protein, mouseCyclamsHeterocyclic CompoundsIndazolesNUCC-390PiperidinesplerixaforPyridinesReceptors, CXCR4

Identifiers

PMID31725979
PMCPMC6917312
OpenAlexW2986082253

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.