Experimental Comparative Effects of Botulinum Toxin A between Subtypes A1 and A2 in Movement Disorders in Rats

T. Kohda, Yasushi Torii, H. Nakajima
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Abstract

In the present review, we describe here experimental comparative and beneficial effects of botulinum neurotoxin A (ANTX) between subtypes A1 and A2 in the pathology of move ment disorders, particularly rat Parkinson’s disease model. We and other laboratories have shown the beneficial effects, and this novel strategy for intractable brain disorders might confer potent and safety therapy in bedside. First, we show the characteristics of ANTXs in the genetic aspects of these subtypes, and our intriguing findings of immunological profiles in the subtypes between A1NTX and A2NTX. Then, we state the distinct diffusion in the body between A1NTX and A2NTX. Importantly, we describe that the intra-brain treatment of small animals with A2NTX subtype results in improvements of pathologies more effectively and provides greater safety than those of A1NTX in a rat 6-OHDA Parkinson’s disease (PD) model. Finally, we represent that the different efficacies between ANTXs are likely due to each localization in the brain; A2NTX is strictly limited in the injected regions, while A1NTX diffused other brain regions. Thus, therapeutic avenue using A2NTX in incurable PD including other movement disorders could be a druggable target in the future.
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A1和A2亚型肉毒毒素A对大鼠运动障碍影响的实验比较
在本综述中,我们描述了A1和A2亚型肉毒杆菌神经毒素A (ANTX)在运动障碍,特别是大鼠帕金森病模型病理中的实验比较和有益作用。我们和其他实验室已经证明了有益的效果,这种治疗顽固性脑部疾病的新策略可能会在床边提供有效和安全的治疗。首先,我们展示了antx在这些亚型的遗传方面的特征,以及我们在A1NTX和A2NTX亚型之间的免疫学特征的有趣发现。然后,我们陈述了A1NTX和A2NTX在体内的不同扩散。重要的是,我们描述了A2NTX亚型小动物脑内治疗在大鼠6-OHDA帕金森病(PD)模型中比A1NTX更有效地改善了病理,并提供了更高的安全性。最后,我们认为antx之间的不同效果可能是由于大脑中的每个位置;A2NTX严格局限于注射区,而A1NTX可扩散至其他脑区。因此,使用A2NTX治疗包括其他运动障碍在内的不治之症可能是未来的一个可药物靶点。
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