Duregotti Elisa, Negro Samuele, Scorzeto Michele, Zornetta Irene, Dickinson Bryan C, Chang Christopher J, Montecucco Cesare, Rigoni Michela
Department of Biomedical Sciences, University of Padua, Padua 35131, Italy;
Department of Chemistry and Molecular and Cell Biology and Howard Hughes Medical Institute, University of California, Berkeley, CA 94720; and.
Proc Natl Acad Sci U S A. 2015 Feb 3;112(5):E497-505. doi: 10.1073/pnas.1417108112. Epub 2015 Jan 20.
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.
一些动物的突触前神经毒素可诱导急性且高度可重复的运动轴突终末变性，随后完全再生，这代表了一个合适且可控的系统，用于剖析外周神经终末变性和再生的分子机制。我们之前已经表明，暴露于蜘蛛或蛇突触前神经毒素的神经终末会因钙超载和线粒体功能障碍而变性。在这里，我们表明经毒素处理的原代神经元会释放源自线粒体的信号分子：过氧化氢、线粒体DNA和细胞色素c。这些分子通过丝裂原活化蛋白激酶（MAPK）途径激活分离的原代施万细胞、与神经元共培养的施万细胞以及体内神经肌肉接头处的施万细胞。我们提出，这种细胞间和细胞内信号传导参与触发受其他形式神经退行性疾病影响的外周神经终末的再生。
