Oral zinc reduces amyloid burden in Tg2576 mice.
Oral zinc reduces amyloid burden in Tg2576 mice.
复制标题
口服锌减轻了TG2576小鼠的淀粉样蛋白负担。
DOI：
10.3233/jad-131703
复制
发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Quinn JF
中科院分区：
文献类型：
--
作者：
Harris CJ;Voss K;Murchison C;Ralle M;Frahler K;Carter R;Rhoads A;Lind B;Robinson E;Quinn JF
阿尔茨海默病中β淀粉样蛋白的聚集可能受到大脑中铜和锌等游离过渡金属的影响。添加铜和锌与淀粉样蛋白可以增加聚集，并且铜还可以促进活性氧的形成。我们提出，通过阻止饮食中铜的摄取来减少脑铜含量是调节 Tg2576 小鼠大脑中不溶性淀粉样蛋白 β 形成的可行策略。小鼠在其生命周期的不同时期接受醋酸锌治疗，醋酸锌与金属硫蛋白一起作用，阻止肠道对铜的吸收，以模拟预防和治疗范例。我们发现，在六个月的研究过程中，小鼠对醋酸锌的耐受性良好。虽然我们没有观察到认知和行为的显着变化，但大脑中不溶性淀粉样蛋白有所减少。这一观察结果与脑铜的减少同时发生，有趣的是脑锌没有变化。我们的研究结果表明，阻止从饮食中摄取铜可以重新分配大脑中的铜并减少β淀粉样蛋白的聚集。
The aggregation of amyloid beta in Alzheimer’s disease can be affected by free transition metals such as copper and zinc in the brain. Addition of copper and zinc with amyloid acts to increase aggregation and copper additionally promotes the formation of reactive oxygen species. We propose that reduction of brain copper by blocking uptake of copper from the diet is a viable strategy to regulate the formation of insoluble amyloid beta in the brain of Tg2576 mice. Mice were treated with regimens of zinc acetate, which acts with metallothionein to block copper uptake in the gut, at various times along their lifespan to model prevention and treatment paradigms. We found that the mice tolerated zinc acetate well over the six month course of study. While we did not observe significant changes in cognition and behavior, there was a reduction in insoluble amyloid beta in the brain. This observation coincided with a reduction in brain copper and interestingly no change in brain zinc. Our findings show that blocking copper uptake from the diet can redistribute copper from the brain and reduce amyloid beta aggregation.