《生命科学》 2012, 24(8): 833-846

脑锌代谢与阿尔茨海默病

郑　玮，王占友^*

(中国医科大学基础医学院病理生理学教研室，沈阳 110001)

摘　要：

摘　要：锌是中枢神经系统含量最丰富的过渡金属元素之一，对维持中枢神经系统正常生理功能具有重要作用，其稳态失衡与多种疾病有关。阿尔茨海默病是一种多病因神经退行性疾病，以β- 淀粉样斑块形成和神经原纤维缠结为主要病理特征。研究表明，脑锌代谢紊乱在阿尔茨海默病发病过程中扮演重要角色，但确切机制尚不十分清楚。综述了脑锌代谢和稳态调控以及锌和锌转运蛋白参与β- 淀粉样蛋白沉积与老年斑形成的病理过程，并探讨了金属- 蛋白阻尼复合物如何通过恢复脑锌稳态延缓疾病进程、改善患者认知能力的治疗策略。

    

关键词：阿尔茨海默病；锌；ZnTs ；ZIPs ；金属硫蛋白；β- 淀粉样蛋白；Tau 蛋白；金属- 蛋白阻尼复合物

    

中图分类号：Q581; R742 文献标志码：A

收稿日期：2012-04-19
基金项目：国家自然科学基金项目(81071004， 81000468)
*通信作者：E-mail: wangzy@mail.cmu.edu.cn

Brain zinc metabolism and Alzheimer’s disease

ZHENG Wei， WANG Zhan-You^*

(Department of Pathophysiology， College of Basic Medical Science， China Medical University， Shenyang 110001， China)

Abstract:
Abstract: Zinc， an essential trace metal in the central nervous system， has numerous biological functions. Alzheimer’s disease (AD) is a multifactorial neurodegenerative disease associated with pathological accumulation of amyloid plaques and with the appearance of deposit of neurofibrillary tangles. Although many studies have demonstrated that disruption of zinc homeostasis is involved in the pathogenesis of AD， the exact role of zinc in the progression of AD remains unclear. In this review， we focus on current advances in brain zinc metabolism in the processing of amyloid-β peptide generation and aggregation. Furthermore， we discuss how therapeutic strategies aimed at restoring brain zinc homeostasis could delay and modify the progression of AD.
Key words: Alzheimer’s disease; zinc; zinc transporters; Zrt/Irt-like proteins; metallothioneins; amyloid-β; Tau;metal-protein attenuating compounds