THE STRUCTURE AND FUNCTION OF PARDAXIN

Pardaxins are polypeptide pore-forming neurotoxins that alter cell plasma membrane permeability by packaging of the hydrophobic, amphipathic α-helices and assembly in the plasma membrane in oligomeric, poorly selective channels. At subcytotoxic concentrations, these small lesions in the plasma membrane induce a sustained increase in intracellular calcium activation, stimulation of the arachidonic acid cascade and massive release of neurotransmitters. These crucial events are further amplified by cascades of cellular signaling, due to the release of local mediators (prostaglandins) and/or neurotransmitters (dopamine) and modifications of intracellular enzymes, ion channels and receptor activities. The end result is a lethal hit to the signal transduction machinery of the attacked cell, resulting in cell death. Elucidation of the neuronal signal transduction pathways affected by pardaxin could provide a new understanding of synaptic transmission and new targets for therapy of patients affected by neurotoxins.