Tetanus toxin (Tetanospasmin) (TeNT)

Tetanus toxin, also known as tetanospasmin, is a highly potent neurotoxin produced by the vegetative cells of Clostridium tetani [4, 5]. It is the primary virulence factor responsible for tetanus, a life-threatening condition characterized by generalized muscle rigidity and violent spasms [18, 19]. The toxin is synthesized as a single 150 kDa polypeptide chain that is subsequently cleaved into a heavy chain (100 kDa) and a light chain (50 kDa) linked by a disulfide bond [5, 13]. The heavy chain mediates high-affinity binding to gangliosides on motor neurons and facilitates the toxin's retrograde transport to the central nervous system, while the light chain functions as a zinc-dependent metalloproteinase [13, 14]. Once inside inhibitory interneurons, the light chain cleaves vesicle-associated membrane protein 2 (VAMP-2/synaptobrevin), effectively blocking the release of inhibitory neurotransmitters such as GABA and glycine [4, 13]. This blockade results in the characteristic over-excitation of motor neurons and painful muscle contractions [5, 18]. Therapeutic strategies involve the use of tetanus immune globulin (TIG) or monoclonal antibodies like siltartoxatug to neutralize the toxin in the circulation before it can bind to neuronal receptors [1, 12, 16].

Other names

TetanospasminTeTxTetanus neurotoxinSpasmogenic toxinTentoxilysin

Neutralization of circulating tetanus toxin to prevent its binding to neuronal gangliosides and subsequent internalization; inhibition of the toxin's zinc-metalloproteinase activity which cleaves VAMP-2/synaptobrevin.