Neuroparalysis and Neuroregeneration Lab

Lab Montecucco members

Description

We study the unique properties of regeneration of the neuromuscular junction (NMJ), after degeneration or paralysis, to discover the signals exchanged among the motor axon terminal, perisynaptic Schwann cells and the muscle fibre leading to its functional recovery.

Degeneration and/or paralysis is induced by mechanical trauma or using presynaptic neurotoxins (including snake phospholipase A2 neurotoxins, the spider α-Latrotoxin or botulinum neurotoxins) which provide good models to discover:

a) the signaling activating the muscle and perisynaptic Schwann cells to promote NMJ rescue

b) the back signaling stimulating the recovery of function of paralysed motor axon terminals

c) the molecular determinants of NMJ plasticity in health and disease

Five recent publications

  • Negro S, Lessi F, Duregotti E, Aretini P, La Ferla M, Franceschi S, Menicagli M, Bergamin E, Radice E, Thelen M, Megighian A, Pirazzini M, Mazzanti CM, Rigoni M, Montecucco C. CXCL12α/SDF-1 from perisynaptic Schwann cells promotes regeneration of injured motor axon terminals. EMBO Mol Med. 2017 Aug;9(8):1000-1010.
  • 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 Feb 3;112(5): E497-505.
  • 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 Sep 25;8(6):1870-1878.
  • Rossetto O, Pirazzini M, Montecucco C. Botulinum neurotoxins: genetic, structural and mechanistic insights. Nat Rev Microbiol. 2014 Aug;12(8):535-49. Review.
  • 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 Jul 15;126(Pt 14):3134-40.