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当代阿耳茨海默病研究

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ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

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Research Article

低剂量卡巴他赛潜力作为微管稳定剂在阿尔茨海默氏病实验模型中的研究：恢复神经元细胞骨架。

卷 17, 期 7, 2020

页: [601 - 615] 页: 15

弟呕挨: 10.2174/1567205017666201007120112

价格: $65

摘要

背景：神经元微管（MT）tau蛋白为神经元细胞提供细胞骨架，起着至关重要的作用，包括维持细胞形状，细胞内运输和细胞分裂。 Tau过度磷酸化介导的MT失稳导致轴突病，另外还有神经递质的缺乏，最终导致阿尔茨海默氏病。临床前，链脲佐菌素（3mg / kg，10μl/单侧，ICV）在立体定位上模仿行为和神经化学改变，类似于阿尔茨海默氏tau病理，导致MT组装缺陷进一步导致神经病理级联。 目的：经临床批准的药物，例如多奈哌齐（DNP），卡巴拉汀和美金刚（MEM）仅负责对症治疗，但没有直接与神经元微管失稳相互作用的特定药理干预措施。 方法：目前的研究集中在低剂量（0.5和2 mg / kg）的抗癌药微管稳定剂卡巴他赛，以及与标准药物DNP（5 mg / kg），MEM（10 mg / kg）的联合治疗中）和微管稳定剂Epothilone D（EpoD）（3 mg / kg）预防脑室内链脲佐菌素（ICV-STZ）中毒的微管相关tau蛋白过度磷酸化。结果：CBZ的长期低剂量单独治疗和与标准药物联合治疗均无副作用，并且通过防止神经元细胞骨架的分解，分别显着改善了认知障碍，神经化学改变以及降低了高磷酸化tau的水平。 结论：以上发现提示低剂量的CBZ对ICV-STZ诱导的大鼠微管相关tau蛋白过度磷酸化具有神经保护作用，可能是预防AD的有效药物。

关键词: 阿尔茨海默氏病，tau蛋白过度磷酸化，微管不稳定，卡巴他赛，多奈哌齐，埃博霉素D.

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