Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.69 (botulinum neurotoxin)
 1,901 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The fact that the fruit and bark of plant belonging to family Melia could be used as digestive tract-parasiticide and agricultural insecticide was recorded about two thousand years ago in ancient China. Toosendanin (TSN, C30H38O11, FW=574), a triterpenoid derivative, was extracted from the bark of Melia toosendan Sieb. et Zucc. by Chinese scientists in 1950os and used as an ascarifuge in China instead of imported sendanin. Studies have demonstrated that TSN possesses special biological actions as well as considerable various values in scientific research, clinic medicine and agriculture. The first is that by interfering with neurotransmitter release by causing an initial facilitation, TSN eventually blocks synaptic transmission at both the neuromuscular junction and central synapses. The action might result from TSN-induced Ca(2+)-sensitivity change and final elimination of transmitter release machinery. The second is that despite sharing many similar actions with botulinum neurotoxin (BoNT) on blocking neuromuscular transmission, TSN has a markedly antibotulismic action in vivo and in vitro: TSN-treatment saves the botulism mice or monkeys from death; TSN-incubation in vitro or TSN-injection in vivo endows neuromuscular junction with a high tolerance to BoNT. Studies suggest that the antibotulismic action is achieved by preventing BoNT from approaching its enzymatic substrate, SNARE protein. The third, in recent years, it is also observed that TSN can induce differentiation and apoptosis in several cell lines, and suppress proliferation of various human cancer cells. The TSN-induced differentiation is Ca(2+)-dependent and the mitochondria-dependent apoptosis pathway is involved in the TSN-induced apoptosis. The fourth is that TSN inhibits various K(+) channels and selectively facilitates Ca(2+) current through L-type Ca(2+) channels and hence elevates [Ca(2+)](i). The TSN-induced [Ca(2+)](i) increase and overload could be responsible for the TSN-induced biphasic effect on neurotransmitter release, cell differentiation, apoptosis as well as the cytotoxicity of TSN.
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PMID:[Biological effects of toosendanin, an active ingredient of herbal vermifuge in Chinese traditional medicine]. 1704 22