title: Understanding the molecular mechanism underlying the presynaptic toxicity of secreted phospholipases A(2): an update.
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.
authors.affiliation: Department of Molecular and Biomedical Sciences, Jožef Stefan Institute, Jamova 39, 1000 Ljubljana, Slovenia.
authors.forename: Jernej
authors.initials: J
authors.lastname: Šribar
authors.affiliation: Department of Molecular and Biomedical Sciences, Jožef Stefan Institute, Jamova 39, 1000 Ljubljana, Slovenia.
authors.forename: Jernej
authors.initials: J
authors.lastname: Oberčkal
authors.affiliation: 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. Electronic address: igor.krizaj@ijs.si.
authors.forename: Igor
authors.initials: I
authors.lastname: Križaj
mesh_terms: D000818:Animals; D020013:Calcium Signaling; D006706:Homeostasis / Q000187:drug effects; D008954:Models, Biological; D009046:Motor Neurons / Q000166:cytology; D009469:Neuromuscular Junction / Q000187:drug effects; D054497:Phospholipases A2, Secretory / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000187:drug effects; D012910:Snake Venoms / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D012910:Snake Venoms; D054497:Phospholipases A2, Secretory
keywords: Mechanism of action; Phospholipase A(2); Presynaptic neurotoxicity; Snake venom