chapter  3
28 Pages

Mechanisms of Actions of Neurotoxins

Clinical symptoms caused by clostridial neurotoxins (CNTs) are due to inhibition of neurotransmitter release and develop subsequent to a multistep process that conveys the enzymatic domain of the disulfide linked di-chain molecule ultimately to the cytosol of certain nerve terminals. The major events that entail intoxication are (1) binding to nerve endings, (2) receptor-mediated internalization of the whole molecule and intracellular vesicular transport to the final site of action of the catalytic domain representing a complex itinerary in the case of tetanus neurotoxin (TeNT), (3) translocation of the catalytic domains from vesicles into the cytosol, (4) reduction of the disulfide bond, and (5) enzymatic conversion of the substrate molecule.