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

Autor: Stazi M; Department of Biomedical Sciences, University of Padova, Padova, Italy., Megighian A; Department of Biomedical Sciences, University of Padova, Padova, Italy., D'Este G; Department of Biomedical Sciences, University of Padova, Padova, Italy., Negro S; Department of Biomedical Sciences, University of Padova, Padova, Italy., Ivanušec A; Department of Molecular and Biomedical Sciences, Jožef Stefan Institute, Ljubljana, Slovenia.; Doctoral School, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia., Lonati D; Pavia Poison Control Centre - National Toxicology Information Centre - Clinical and Experimental Lab, Toxicology Unit, Istituti Clinici Scientifici Maugeri SpA SB IRCCS, Pavia, Italy., Pirazzini M; Department of Biomedical Sciences, University of Padova, Padova, Italy., Križaj I; Department of Molecular and Biomedical Sciences, Jožef Stefan Institute, Ljubljana, Slovenia., Montecucco C; Department of Biomedical Sciences, University of Padova, Padova, Italy.; National Research Council, Institute of Neuroscience, Padova, Italy.
Jazyk: angličtina
Zdroj: Journal of neurochemistry [J Neurochem] 2024 Apr; Vol. 168 (4), pp. 428-440. Date of Electronic Publication: 2023 Mar 27.
DOI: 10.1111/jnc.15803
Abstrakt: People 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 sPLA 2 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.
(© 2023 International Society for Neurochemistry.)
Databáze: MEDLINE
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