慢性马替尼治疗 APPswe/PSEN1dE9 转基因阿尔茨海默病模型小鼠的作用。
Effects of Chronic Masitinib Treatment in APPswe/PSEN1dE9 Transgenic Mice Modeling Alzheimer's Disease.
机构信息
ICM Institut du Cerveau et de la Moelle épinière, CNRS UMR7225, INSERM U1127, Sorbonne Université, Hôpital de la Pitié-Salpêtrière, Paris, France.
CRCM, [Signaling, Hematopoiesis and Mechanism of Oncogenesis, Equipe Labellisée Ligue Contre le Cancer], Inserm, U1068; Institut Paoli-Calmettes; Aix-Marseille Univ, UM105; CNRS, UMR7258, Marseille, France.
出版信息
J Alzheimers Dis. 2020;76(4):1339-1345. doi: 10.3233/JAD-200466.
BACKGROUND
Masitinib is a selective tyrosine kinase inhibitor that modulates mast cells activity. A previous phase II study reported a cognitive effect of masitinib in patients with Alzheimer's disease.
OBJECTIVE
We aimed to shed light on the mode of action of masitinib in Alzheimer's disease.
METHODS/RESULTS: We demonstrated here that chronic oral treatment of APPswe/PSEN1dE9 transgenic mice modeling Alzheimer's disease restored normal spatial learning performance while having no impacts on amyloid-β loads nor on neuroinflammation. However, masitinib promoted a recovery of synaptic markers. Complete genetic depletion of mast cells in APPswe/PSEN1dE9 mice similarly rescued synaptic impairments.
CONCLUSION
These results underline that masitinib therapeutic efficacy might primarily be associated with a synapto-protective action in relation with mast cells inhibition.
背景
马替尼是一种选择性的酪氨酸激酶抑制剂，可调节肥大细胞的活性。先前的一项二期研究报告称，马替尼对阿尔茨海默病患者有认知作用。
目的
我们旨在阐明马替尼在阿尔茨海默病中的作用模式。
方法/结果：我们在这里证明，慢性口服治疗 APPswe/PSEN1dE9 转基因小鼠模型的阿尔茨海默病恢复了正常的空间学习能力，而对淀粉样蛋白-β负荷或神经炎症没有影响。然而，马替尼促进了突触标志物的恢复。在 APPswe/PSEN1dE9 小鼠中完全遗传耗尽肥大细胞也同样挽救了突触损伤。
结论
这些结果表明，马替尼的治疗效果可能主要与抑制肥大细胞有关的突触保护作用有关。
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