An agonist of CXCR4 induces a rapid recovery from the neurotoxic effects of Vipera ammodytes and Vipera aspis venoms

Author:

Stazi M.1,Megighian A.1,D'Este G.1,Negro S.1,Ivanušec A.23,Lonati D.4,Pirazzini M.1,Križaj I.2,Montecucco C.15ORCID

Affiliation:

1. Department of Biomedical Sciences University of Padova Padova Italy

2. Department of Molecular and Biomedical Sciences Jožef Stefan Institute Ljubljana Slovenia

3. Doctoral School, Faculty of Medicine University of Ljubljana Ljubljana Slovenia

4. Pavia Poison Control Centre ‐ National Toxicology Information Centre ‐ Clinical and Experimental Lab, Toxicology Unit Istituti Clinici Scientifici Maugeri SpA SB IRCCS Pavia Italy

5. National Research Council Institute of Neuroscience Padova Italy

Abstract

AbstractPeople bitten by Alpine vipers are usually treated with antivenom antisera to prevent the noxious consequences caused by the injected venom. However, this treatment suffers from a number of drawbacks and additional therapies are necessary. The venoms of Vipera ammodytes and of Vipera aspis are neurotoxic and cause muscle paralysis by inducing neurodegeneration of motor axon terminals because they contain a presynaptic acting sPLA2 neurotoxin. We have recently found that any type of damage to motor axons is followed by the expression and activation of the intercellular signaling axis consisting of the CXCR4 receptor present on the membrane of the axon stump and of its ligand, the chemokine CXCL12 released by activated terminal Schwann cells. We show here that also V. ammodytes and V. aspis venoms cause the expression of the CXCL12‐CXCR4 axis. We also show that a small molecule agonist of CXCR4, dubbed NUCC‐390, induces a rapid regeneration of the motor axon terminal with functional recovery of the neuromuscular junction. These findings qualify NUCC‐390 as a promising novel therapeutics capable of improving the recovery from the paralysis caused by the snakebite of the two neurotoxic Alpine vipers.image

Funder

Javna Agencija za Raziskovalno Dejavnost RS

Università degli Studi di Padova

Publisher

Wiley

Subject

Cellular and Molecular Neuroscience,Biochemistry

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