Understanding the molecular mechanism underlying the presynaptic toxicity of secreted phospholipases A2: An update

• β-ntxs are sPLA2s that inhibit neurotransmission.
• β-neurotoxicity is a receptor-mediated process.
• β-ntxs translocate into the cytosol and mitochondria of the nerve ending.
• Intracellular PLA2 activity of β-ntxs seems to be important for β-neurotoxicity.
• β-ntxs disturb Ca2+ homoeostasis in the nerve ending.

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 Ca2+ 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.