一种降低铜含量的策略可减轻阿尔茨海默病转基因小鼠模型中的淀粉样蛋白病理。
A copper-lowering strategy attenuates amyloid pathology in a transgenic mouse model of Alzheimer's disease.
机构信息
Portland Veterans Affairs Medical Center, P3 R&D, Portland, OR, USA.
出版信息
J Alzheimers Dis. 2010;21(3):903-14. doi: 10.3233/JAD-2010-100408.
Abstract
There is increasing evidence for the crucial role of metals in the pathology of Alzheimer's disease. Both the aggregation and neurotoxicity of amyloid-β are dependent on the presence of copper. This study investigated the ability of the copper-complexing drug tetrathiomolybdate to reduce amyloid-β pathology and spatial memory impairment in both a prevention and a treatment paradigm in the Tg2576 mouse model of Alzheimer's disease. Tetrathiomolybdate treatment lowered brain copper and reduced amyloid-β levels in the prevention paradigm, but not in the treatment paradigm. Our data suggests that controlled lowering of systemic copper may achieve anti-amyloid effects if initiated early in the disease process.
摘要
越来越多的证据表明金属在阿尔茨海默病的病理学中起着关键作用。淀粉样蛋白-β的聚集和神经毒性都依赖于铜的存在。本研究在阿尔茨海默病的 Tg2576 小鼠模型中，通过预防和治疗两种模式，研究了铜络合剂四硫钼酸盐降低淀粉样蛋白-β病理学和空间记忆障碍的能力。在预防模式中，四硫钼酸盐处理降低了大脑中的铜含量并降低了淀粉样蛋白-β水平，但在治疗模式中则没有。我们的数据表明，如果在疾病早期开始，系统铜的受控降低可能会产生抗淀粉样蛋白的效果。
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