Botulinum toxin type a là gì? Các công bố khoa học về Botulinum toxin type a

The labeling patterns produced by radioiodinated botulinum neurotoxin (125I-BoNT) types A and B at the vertebrate neuromuscular junction were investigated using electron microscopic autoradiography. The data obtained allow the following conclusions to be made. 125I-BoNT type A, applied in vivo or in vitro to mouse diaphragm or frog cutaneous pectoris muscle, interacts saturably with the motor nerve terminal only; silver grains occur on the plasma membrane, within the synaptic bouton, and in the axoplasm of the nerve trunk, suggesting internalization and retrograde intra-axonal transport of toxin or fragments thereof. 125I-BoNT type B, applied in vitro to the murine neuromuscular junction, interacts likewise with the motor nerve terminal except that a lower proportion of internalized radioactivity is seen. This result is reconcilable with the similar, but not identical, pharmacological action of these toxin types. The saturability of labeling in each case suggested the involvement of acceptors; on preventing the internalization step with metabolic inhibitors, their precise location became apparent. They were found on all unmyelinated areas of the nerve terminal membrane, including the preterminal axon and the synaptic bouton. Although 125I-BoNT type A interacts specifically with developing terminals of newborn rats, the unmyelinated plasma membrane of the nerve trunk is not labeled, indicating that the acceptors are unique components restricted to the nerve terminal area. BoNT types A and B have distinct acceptors on the terminal membrane. Having optimized the conditions for saturation of these binding sites and calibrated the autoradiographic procedure, we found the densities of the acceptors for types A and B to be approximately 150 and 630/micron 2 of membrane, respectively. It is proposed that these membrane acceptors target BoNT to the nerve terminal and mediate its delivery to an intracellular site, thus contributing to the toxin's selective inhibitory action on neurotransmitter release.

Tetanus and botulinum neurotoxins selectively invade neurons following binding to complex gangliosides. Recent biochemical experiments demonstrate that two ganglioside binding sites within the tetanus neurotoxin H_C‐fragment, originally identified in crystallographic studies to bind lactose or sialic acid, are required for productive binding to target cells. Here, we determine by mass spectroscopy studies that the H_C‐fragment of botulinum neurotoxins A and B bind only one molecule of ganglioside GT1b. Mutations made in the presumed ganglioside binding site of botulinum neurotoxin A and B abolished the formation  of  these  H_C‐fragment/ganglioside  complexes, and drastically diminished binding to neuronal membranes and isolated GT1b. Furthermore, correspondingly mutated full‐length neurotoxins exhibit significantly reduced neurotoxicity, thus identifying a single ganglioside binding site within the carboxyl‐terminal half of the H_C‐fragment of botulinum neurotoxins A and B. These binding cavities are defined by the conserved peptide motif H…SXWY…G. The roles of tyrosine and histidine in botulinum neurotoxins A and B in ganglioside binding differ from those in the analogous tetanus neurotoxin lactose site. Hence, these findings provide valuable information for the rational design of potent botulinum neurotoxin binding inhibitors.

We studied the safety and efficacy of 0 U, 50 U, 100 U, 150 U (five sites), 86 Usub and 100 Usub (three sites) botulinum toxin type A (BoNTA; BOTOX^®; Allergan, Inc., Irvine, CA, USA) for the prophylaxis of chronic tension-type headache (CTTH). Three hundred patients (62.3± female; mean age 42.6 years) enrolled. For the primary endpoint, the mean change from baseline in the number of TTH-free days per month, there was no statistically significant difference between placebo and four BoNTA groups, but a significant difference favouring placebo vs. BoNTA 150 was observed (4.5 vs. 2.8 tension headache-free days/month; P = 0.007). All treatment groups improved at day 60. Although efficacy was not demonstrated for the primary endpoint, at day 90, more patients in three BoNTA groups had ≥50± decrease in tension headache days than did placebo ( P ≤ 0.024). Most treatment-related adverse events were mild or moderate, and transient. BoNTA was safe and well-tolerated in the study.