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肉毒杆菌神经毒素的工业生产与治疗应用:A型的作用

Industrial Production and Therapeutic Application of Botulinum Neurotoxin: The Role of Type A.

作者信息

Kadir S Danish

机构信息

Department of Biochemistry and Molecular Biology, The University of Texas Rio Grande Valley, Edinburg, Texas, USA.

出版信息

Pharm Nanotechnol. 2024;12(2):99-107. doi: 10.2174/2211738511666230825150259.

Abstract

Botulinum neurotoxin has remarkably transitioned from a food safety hazard and biological warfare to an effective therapeutic drug. Currently, botulinum neurotoxins have seven serotypes (BoNT/A-G) in the form of protein complexes produced by , a gram-positive and sporeforming bacteria. The conversion of toxins into useful drug substances of choice using the biotechnological process is tremendously increasing. Recent studies have shown that Botulinum neurotoxin-A (BoNT/A) has different biological activities and potencies in experimental and clinical conditions. They also indicate that the manufacturing process influences the potency and efficacy of BoNT/A drugs. Thus, this review focuses on the following criteria: detailed Fed-batch operation that includes the upstream and downstream processing of BoNT/A, the underlying mechanism behind the neurotoxic effect, and commercially available FDA-approved BoNT/A products and their therapeutic uses. Still, some research gaps exist in the mechanism for the treatment of psychiatric disorders.

摘要

肉毒杆菌神经毒素已从食品安全危害和生物战剂显著转变为一种有效的治疗药物。目前,肉毒杆菌神经毒素有七种血清型(BoNT/A - G),以革兰氏阳性产芽孢细菌产生的蛋白质复合物形式存在。利用生物技术过程将毒素转化为有用的药物选择的情况正在大幅增加。最近的研究表明,肉毒杆菌神经毒素A(BoNT/A)在实验和临床条件下具有不同的生物学活性和效力。这些研究还表明,生产过程会影响BoNT/A药物的效力和疗效。因此,本综述聚焦于以下标准:包括BoNT/A上下游加工的详细分批补料操作、神经毒性作用背后的潜在机制、以及美国食品药品监督管理局(FDA)批准的市售BoNT/A产品及其治疗用途。不过,在精神疾病治疗机制方面仍存在一些研究空白。

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