Neurotoxins, Neuroparalysis and Regeneration

Lab Montecucco members

 

Description

We study the mechanism of action of several bacterial and animal presynaptic neurotoxins as a mean to discover fundamental physiological aspects of the synaptic transmission, including the structure of the neuroexocytosis nanomachine.
We use some presynaptic neurotoxins that cause a complete, but reversible, degeneration of peripheral nerve terminals as a model to discover: a) the signaling used by the decaying nerve terminals to activate the muscle, perisynaptic Schwann cells and innate immune cells and b) the back signaling used by these latter cells to induce the re-growth of the nerve terminal.

5 Selected papers

  • Rossetto O., Pirazzini M., Montecucco C. Botulinum neurotoxins: recent genetic, structural and mechanistic insights Nat. Rev. Microbiol. (2014),12(8):535-549.
  • Duregotti E, Negro S, Scorzeto M, Zornetta I, Dickinson BC, Chang CJ, Montecucco C, Rigoni M. Mitochondrial alarmins released by degenerating motor axon terminals activate perisynaptic Schwann cells. Proc Natl Acad Sci U S A.(2015) 112(5):E497-505. 
  • Megighian A, Zordan M, Pantano S, Scorzeto M, Rigoni M, Zanini D, Rossetto O, Montecucco C. Evidence for a radial SNARE super-complex mediating neurotransmitter release at the Drosophila neuromuscular junction. J Cell Sci. (2013) 126:3134-40.
  • Colasante C, Morbiato L., Rossetto O, Pirazzini M, Molgo J. and Montecucco C. Botulinum Neurotoxin type A is Internalized and Translocates from Small Synaptic Vesicles at the Neuromuscular Junction. Mol. Neurobiol. (2013), 48:120-127.
  • Pirazzini M, Azarnia Tehran D, Zanetti G, Megighian A, Scorzeto M, Fillo S, Shone CC, Binz T, Rossetto O, Lista F, Montecucco C. Thioredoxin and its reductase are present on synaptic vesicles, and their inhibition prevents the paralysis induced by botulinum neurotoxins. Cell Rep. (2014), 8(6):1870-8.

 

Funding bodies

  • University of Padova,
  • Italian Ministry of University and Research, Ministry of Health, Ministry of Defence,
  • Fondazione CARIPARO
  • Provincia Autonoma di Trento