Isoforms of SNARE molecules and their use in regulating cellular exocytosis

摘要

A method of treating a patient suffering from poisoning by clostridial toxin wherein a SNARE (soluble (iN/i-ethylmaleimide-sensitive fusion protein)-attachment protein receptor) that is resistant to proteolysis by the said clostridial toxin (toxin-resistant SNARE) and/or is capable of inhibiting the clostridial toxin is supplied to a cell of the patient. The SNARE that is resistant to proteolysis may be, synaptosomal-associated polypeptide of 25 kDA (SNAP-25). The SNAP-25 is preferably resistant to proteolysis by BoNT/A, BoNT/E and BoNT/C. A method of treating a patient in need of inhibition of SNARE-dependent exocytosis from a cell capable of performing SNARE-dependent exocytosis wherein a derivative (inhibitory SNARE) that is capable of inhibiting SNARE-dependent exocytosis is supplied to the said cell of the patient. The inhibitory SNARE may be a fragment of SNAP-25 that is derivable by cleavage of SNAP-25 by botulinum toxin A (BoNT/A). The cell may be, for example, a nerve cell, adreno-chromaffin cell or insulin-secreting cell. The SNARE may be supplied to the cell by expressing recombinant polynucleotide construct. The SNARE or construct may be targeted to a nerve cell, by means of an inactive clostridial neurotoxin. The SNARE may be expressed under the target cell-specific promoter.