title: Mitochondrial alarmins released by degenerating motor axon terminals activate perisynaptic Schwann cells.
abstract: An acute and highly reproducible motor axon terminal degeneration followed by complete regeneration is induced by some animal presynaptic neurotoxins, representing an appropriate and controlled system to dissect the molecular mechanisms underlying degeneration and regeneration of peripheral nerve terminals. We have previously shown that nerve terminals exposed to spider or snake presynaptic neurotoxins degenerate as a result of calcium overload and mitochondrial failure. Here we show that toxin-treated primary neurons release signaling molecules derived from mitochondria: hydrogen peroxide, mitochondrial DNA, and cytochrome c. These molecules activate isolated primary Schwann cells, Schwann cells cocultured with neurons and at neuromuscular junction in vivo through the MAPK pathway. We propose that this inter- and intracellular signaling is involved in triggering the regeneration of peripheral nerve terminals affected by other forms of neurodegenerative diseases.
authors.affiliation: Department of Biomedical Sciences, University of Padua, Padua 35131, Italy;
authors.forename: Elisa
authors.initials: E
authors.lastname: Duregotti
authors.affiliation: Department of Biomedical Sciences, University of Padua, Padua 35131, Italy;
authors.forename: Samuele
authors.initials: S
authors.lastname: Negro
authors.affiliation: Department of Biomedical Sciences, University of Padua, Padua 35131, Italy;
authors.forename: Michele
authors.initials: M
authors.lastname: Scorzeto
authors.affiliation: Department of Biomedical Sciences, University of Padua, Padua 35131, Italy;
authors.forename: Irene
authors.initials: I
authors.lastname: Zornetta
authors.affiliation: Department of Chemistry and Molecular and Cell Biology and Howard Hughes Medical Institute, University of California, Berkeley, CA 94720; and.
authors.forename: Bryan C
authors.initials: BC
authors.lastname: Dickinson
authors.affiliation: Department of Chemistry and Molecular and Cell Biology and Howard Hughes Medical Institute, University of California, Berkeley, CA 94720; and.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Chang
authors.affiliation: Department of Biomedical Sciences, University of Padua, Padua 35131, Italy; Italian National Research Council Institute of Neuroscience, Padua 35131, Italy michela.rigoni@unipd.it cesare.montecucco@unipd.it.
authors.forename: Cesare
authors.initials: C
authors.lastname: Montecucco
authors.affiliation: Department of Biomedical Sciences, University of Padua, Padua 35131, Italy; michela.rigoni@unipd.it cesare.montecucco@unipd.it.
authors.forename: Michela
authors.initials: M
authors.lastname: Rigoni
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D018920:Coculture Techniques; D045304:Cytochromes c / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D009498:Neurotoxins / Q000378:metabolism*; D010587:Phagocytosis; D012583:Schwann Cells / Q000378:metabolism*; D012911:Snakes; D013112:Spiders; D013569:Synapses / Q000378:metabolism*
chemical_list: D004272:DNA, Mitochondrial; D009498:Neurotoxins; D045304:Cytochromes c
keywords: Schwann cells; mitochondrial alarmins; motor axon degeneration; presynaptic neurotoxins