用铜锌螯合剂治疗可显著且迅速地抑制阿尔茨海默病转基因小鼠中β-淀粉样蛋白的积累。

Treatment with a copper-zinc chelator markedly and rapidly inhibits beta-amyloid accumulation in Alzheimer's disease transgenic mice.

作者信息

Cherny R A, Atwood C S, Xilinas M E, Gray D N, Jones W D, McLean C A, Barnham K J, Volitakis I, Fraser F W, Kim Y, Huang X, Goldstein L E, Moir R D, Lim J T, Beyreuther K, Zheng H, Tanzi R E, Masters C L, Bush A I

机构信息

Department of Pathology, The University of Melbourne and, The Mental Health Research Institute of Victoria, Australia.

出版信息

Neuron. 2001 Jun;30(3):665-76. doi: 10.1016/s0896-6273(01)00317-8.

DOI:10.1016/s0896-6273(01)00317-8

PMID:11430801

Abstract

Inhibition of neocortical beta-amyloid (Abeta) accumulation may be essential in an effective therapeutic intervention for Alzheimer's disease (AD). Cu and Zn are enriched in Abeta deposits in AD, which are solubilized by Cu/Zn-selective chelators in vitro. Here we report a 49% decrease in brain Abeta deposition (-375 microg/g wet weight, p = 0.0001) in a blinded study of APP2576 transgenic mice treated orally for 9 weeks with clioquinol, an antibiotic and bioavailable Cu/Zn chelator. This was accompanied by a modest increase in soluble Abeta (1.45% of total cerebral Abeta); APP, synaptophysin, and GFAP levels were unaffected. General health and body weight parameters were significantly more stable in the treated animals. These results support targeting the interactions of Cu and Zn with Abeta as a novel therapy for the prevention and treatment of AD.

摘要

抑制新皮质β-淀粉样蛋白（Aβ）的积累可能是阿尔茨海默病（AD）有效治疗干预的关键所在。铜和锌在AD患者的Aβ沉积物中含量丰富，在体外可被铜/锌选择性螯合剂溶解。在此，我们报告一项针对APP2576转基因小鼠的双盲研究结果，这些小鼠口服氯碘羟喹（一种抗生素及可生物利用的铜/锌螯合剂）9周后，脑内Aβ沉积减少了49%（降至-375微克/克湿重，p = 0.0001）。与此同时，可溶性Aβ略有增加（占总脑Aβ的1.45%）；APP、突触素和GFAP水平未受影响。接受治疗的动物总体健康状况和体重参数明显更稳定。这些结果支持将针对铜和锌与Aβ的相互作用作为预防和治疗AD的一种新疗法。