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在AD小鼠模型中,分析氨酸激酶抑制剂作为AD治疗药物

Hyun-Ju Lee¹, Jeong-Woo Hwang², Jin-Hee Park^2,3

¹Department of Neural Development and Disease, Korea Brain Research Institute (KBRI), 61, Cheomdan-ro, Daegu, 41068, Republic of Korea. hjlee@kbri.re.kr.

Molecular brain

|August 14, 2023

概括

并非所有氨酸激酶抑制剂 (TKI) 都能有效地治疗老鼠模型中的阿尔茨海默病 (AD) 病理. 易布鲁替尼布显示了治疗效益,而PD180970恶化了tau病理,卡博桑提尼布的结果不一,突出了需要仔细选择药物.

科学领域:

神经科学是一个神经科学.
药理学药理学是指药理学的学科.
生物化学生物化学

背景情况:

阿尔茨海默病 (AD) 涉及粉样β (Aβ) 斑块,病,神经炎症和认知能力下降.
蛋白激酶越来越多地与阿尔茨海默病理有关,使得氨酸激酶抑制剂 (TKI) 成为潜在的治疗候选者.

研究的目的:

调查三种TKIibrutinib,PD180970和cabozantinib对5xFAD小鼠早期AD病理学的选择性影响.
为了确定不同的TKI是否对阿尔茨海默病具有不同的治疗潜力.

主要方法:

使用易布鲁丁尼布,PD180970或卡博桑提尼布 (10 mg/kg,I.P.) 在5xFAD小鼠中.
评估Aβ斑块负载,高酸化,神经炎症和星病.
对抗阿尔茨海默病的标志性特征的测试TKI治疗疗效的比较.

主要成果:

易布鲁替尼显著降低了Aβ斑块数量,陶过酸化和神经炎症.
PD180970未能改变Aβ斑块或神经炎症,但加剧了陶过酸化.
卡博桑提尼布对粉样蛋白病变没有影响,但部分降低了陶过酸化和星球化.

结论:

在阿尔茨海默病小鼠模型中TKIs的治疗疗效不是普遍的.
药物优化,包括剂量,时间和施用途径,对于将TKI重新定位为AD疗法至关重要.

关键词:

阿尔茨海默氏症是阿尔茨海默氏症的一种疾病.粉样蛋白-β 是一种卡博桑提尼布 (Cabozantinib) 是一种药物.易布鲁丁尼布的使用方法神经炎症是一种神经炎症.PD18097070 这是一个很大的问题.塔乌·塔乌 (Tau Tau) 是一个铁氨酸激酶抑制剂铁氨酸激酶抑制剂

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