Duregotti Elisa, Zanetti Giulia, Scorzeto Michele, Megighian Aram, Montecucco Cesare, Pirazzini Marco, Rigoni Michela
Department of Biomedical Sciences, University of Padua, Via U. Bassi 58/B, 35131 Padova, Italy.
Institute for Neuroscience, National Research Council, Via U. Bassi 58/B, 35131 Padova, Italy.
Toxins (Basel). 2015 Dec 8;7(12):5322-36. doi: 10.3390/toxins7124887.
Botulinum neurotoxins (BoNTs) and some animal neurotoxins (β-Bungarotoxin, β-Btx, from elapid snakes and α-Latrotoxin, α-Ltx, from black widow spiders) are pre-synaptic neurotoxins that paralyse motor axon terminals with similar clinical outcomes in patients. However, their mechanism of action is different, leading to a largely-different duration of neuromuscular junction (NMJ) blockade. BoNTs induce a long-lasting paralysis without nerve terminal degeneration acting via proteolytic cleavage of SNARE proteins, whereas animal neurotoxins cause an acute and complete degeneration of motor axon terminals, followed by a rapid recovery. In this study, the injection of animal neurotoxins in mice muscles previously paralyzed by BoNT/A or /B accelerates the recovery of neurotransmission, as assessed by electrophysiology and morphological analysis. This result provides a proof of principle that, by causing the complete degeneration, reabsorption, and regeneration of a paralysed nerve terminal, one could favour the recovery of function of a biochemically- or genetically-altered motor axon terminal. These observations might be relevant to dying-back neuropathies, where pathological changes first occur at the neuromuscular junction and then progress proximally toward the cell body.
肉毒杆菌神经毒素（BoNTs）和一些动物神经毒素（来自眼镜蛇科蛇类的β-银环蛇毒素，β-Btx，以及来自黑寡妇蜘蛛的α- latrotoxin，α-Ltx）是突触前神经毒素，它们会使运动轴突终末麻痹，在患者身上产生相似的临床结果。然而，它们的作用机制不同，导致神经肌肉接头（NMJ）阻断的持续时间有很大差异。BoNTs通过对SNARE蛋白进行蛋白水解切割，诱导持久麻痹且不会导致神经终末变性，而动物神经毒素会导致运动轴突终末急性完全变性，随后迅速恢复。在本研究中，向先前被BoNT/A或/B麻痹的小鼠肌肉中注射动物神经毒素，通过电生理学和形态学分析评估，可加速神经传递的恢复。这一结果提供了一个原理证明，即通过引起麻痹神经终末的完全变性、重吸收和再生，有可能促进生化或基因改变的运动轴突终末的功能恢复。这些观察结果可能与轴索性神经病相关，在轴索性神经病中，病理变化首先发生在神经肌肉接头，然后向近端朝着细胞体发展。
