Ceruloplasmin dysfunction and therapeutic potential for Parkinson disease
Ceruloplasmin dysfunction and therapeutic potential for Parkinson disease
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DOI：
10.1002/ana.23817
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发表时间：
2013-04-01
影响因子：
11.2
通讯作者：
Finkelstein, David I.
中科院分区：
文献类型：
--
作者：
Ayton, Scott;Lei, Peng;Finkelstein, David I.
铜蓝蛋白是一种铁输出铁氧化酶，在血浆中含量丰富，也在神经胶质细胞中表达。我们发现在特发性帕金森病（PD）病例的黑质中，铜蓝蛋白铁氧化酶活性损失约80%，这可能有助于病理学特征的促氧化剂铁积累。与血浆铜蓝蛋白在PD发病机制中的作用一致，血浆铜蓝蛋白敲除小鼠发展为帕金森综合征，其通过铁螯合而被拯救。此外，外周输注铜蓝蛋白可减轻1-甲基-4-苯基-1，2，3，6-四氢吡啶小鼠PD模型中的神经变性和黑质铁升高。这些结果表明，原则上，静脉铜蓝蛋白可能有治疗PD的潜力。《神经病学年鉴》2013;73：554-559
Ceruloplasmin is an iron-export ferroxidase that is abundant in plasma and also expressed in glia. We found a approximate to 80% loss of ceruloplasmin ferroxidase activity in the substantia nigra of idiopathic Parkinson disease (PD) cases, which could contribute to the pro-oxidant iron accumulation that characterizes the pathology. Consistent with a role for ceruloplasmin in PD etiopathogenesis, ceruloplasmin knockout mice developed parkinsonism that was rescued by iron chelation. Additionally, peripheral infusion of ceruloplasmin attenuated neurodegeneration and nigral iron elevation in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model for PD. These findings show, in principle, that intravenous ceruloplasmin may have therapeutic potential in PD. Ann Neurol 2013;73:554-559