分泌型磷脂酶A(2)突触前毒性的分子机制解析：最新进展

Understanding the molecular mechanism underlying the presynaptic toxicity of secreted phospholipases A(2): an update.

作者信息

Šribar Jernej, Oberčkal Jernej, Križaj Igor

机构信息

Department of Molecular and Biomedical Sciences, Jožef Stefan Institute, Jamova 39, 1000 Ljubljana, Slovenia.

Department of Molecular and Biomedical Sciences, Jožef Stefan Institute, Jamova 39, 1000 Ljubljana, Slovenia; Department of Chemistry and Biochemistry, Faculty of Chemistry and Chemical Technology, University of Ljubljana, Aškerčeva 5, SI-1000 Ljubljana, Slovenia.

出版信息

Toxicon. 2014 Oct;89:9-16. doi: 10.1016/j.toxicon.2014.06.019. Epub 2014 Jul 5.

DOI:10.1016/j.toxicon.2014.06.019

PMID:25009088

Abstract

β-neurotoxins are enzymes, secreted phospholipases A2, that inhibit neurotransmission in neuromuscular synapses by poisoning the motoneuron. They were reviewed extensively several years ago (Pungerčar and Križaj, 2007). Here we present and critically discuss the most important experimental facts reported since then. Evidence has been presented for specific internalization of β-neurotoxins into the nerve endings of motoneurons, their in vivo binding to some cytosolic proteins, direct action on mitochondria, disruption of Ca(2+) homoeostasis and inhibition of amphiphysin function. New insights have led to a more confident interpretation of the action of these toxins at the molecular level. The most important questions that remain to be answered are listed.

摘要

β-神经毒素是一类酶，即分泌型磷脂酶A2，通过毒害运动神经元来抑制神经肌肉突触中的神经传递。几年前已有对它们的广泛综述（Pungerčar和Križaj，2007年）。在此，我们呈现并批判性地讨论自那时以来报道的最重要的实验事实。已有证据表明β-神经毒素可特异性内化至运动神经元的神经末梢，它们在体内与某些胞质蛋白结合，直接作用于线粒体，破坏Ca(2+)稳态并抑制发动蛋白功能。新的见解使人们对这些毒素在分子水平上的作用有了更可靠的解释。文中列出了仍有待解答的最重要问题。