Bagetta G, Nisticò G
Faculty of Pharmacy, University of Calabria, Cosemza, Italy.
Pharmacol Ther. 1994 Apr-May;62(1-2):29-39. doi: 10.1016/0163-7258(94)90003-5.
Tetanus toxin is a potent clostridial neurotoxin responsible for causing spastic paralysis in humans, often accompanied by seizures and death. The tetanic syndrome is believed to originate from a disinhibitory action of the toxin in the CNS. To produce its effects, tetanus toxin undergoes retrograde, intra-axonal transport to the CNS, where it blocks preferentially the release of gamma-aminobutyric acid and glycine, two inhibitory neurotransmitters. These effects stem from the cleavage of synaptobrevin, a constitutive small-vesicle protein, by tetanus toxin, whose zinc-dependent metalloprotease characteristics recently have been recognized. Blockade of inhibitory transmission produces a predominance of excitatory amino acid neurotransmission, which is responsible for the neurodegenerative effect caused by tetanus toxin after intrahippocampal injection in rats. In fact, hippocampal damage can effectively be prevented by reduction of glutamate-mediated excitatory transmission, thus suggesting that unopposed excitation may be the underlying mechanism for neuronal cell death.
破伤风毒素是一种强效的梭菌神经毒素，可导致人类发生痉挛性麻痹，常伴有癫痫发作和死亡。破伤风综合征被认为源于该毒素在中枢神经系统中的去抑制作用。为发挥其作用，破伤风毒素会进行逆行性轴突内运输至中枢神经系统，在那里它优先阻断γ-氨基丁酸和甘氨酸这两种抑制性神经递质的释放。这些作用源于破伤风毒素对突触囊泡蛋白（一种组成型小泡蛋白）的切割，其锌依赖性金属蛋白酶特性最近已得到确认。抑制性传递的阻断导致兴奋性氨基酸神经传递占主导，这是大鼠海马内注射破伤风毒素后造成神经退行性效应的原因。事实上，通过减少谷氨酸介导的兴奋性传递可有效预防海马损伤，因此表明无对抗的兴奋可能是神经元细胞死亡的潜在机制。
