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Recombinant botulinum neurotoxin a heavy chain-based delivery vehicles for neuronal cell targeting

摘要篇首: Botulinum neurotoxin has been used in cosmetic wrinkle remomaland with a variety of medical procedures, but botulism toxin poisoning (Botulism) is anextremely dangerousconditionand islife-threatening.Because the bacteria produce a neurotoxin that could enter the nerve terminal, obstruct neuromuscular signal transmission. Botulinum neurotoxin type A (BoNT / A) in nerve cells of has a half-life of up to several months, and patients with botulism could require a period of up to one year for complete recovery. The persistence ofneurotoxin inside neuronspresents great challenges in developing treatment strategies that complement the existing anti-toxin therapy. Existing anti-toxin antibodies can prevent additional toxin moleculesfrom entering the nerve cells andfacilitate clearance of toxin from the circulatory. However, once toxin molecules are inside the cells, these antibodies will have no effect. As a treatment strategy, low molecular weight inhibitors may penetrate into the cells but the lack of target cell selectivity limits their effectiveness. Protein carders that recognize specific receptors on target cells can be used to provide the availability of drugs for specific nerve cells. Botulinum neurotoxin type A is a double-chiainprotein molecule.Its light chain (LC) is the activity domain housing the toxicity, and its heavy chain (HC) consists of the receptor-binding domain (BD) and the translocation domain (TD). Delivery vehicles consisting of the toxin heavy chain (HC), including the receptor-binding domain (BD) and translocation domain (TD), connected to an inhibitory cargo offer a possible solution for rescuing intoxicated neurons in victims paralyzed from botulism.

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