期刊
MOLECULAR BRAIN
卷 12, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s13041-019-0528-2
关键词
Zinc transporter; Brain; Genetic modulation; Emerging therapeutic target; Alzheimer's disease; Ageing
资金
- National Natural Science Foundation of China [31571042, 31671284]
- Special Fund for University Teachers and the Institute for Scientific Research Cooperation at the Chinese Academy of Sciences [Y55201BY00]
- Hundreds of Excellent Innovative Talents in Hebei Province Support Plan II [BR2-218]
- National Postdoctoral Program for Innovative Talents [BX201600045]
- Fundamental Research Funds for the Central Universities [PA2017GDQT0018]
Alzheimer's disease (AD) is the most devastating neurodegenerative disorder. Due to the increase in population and longevity, incidence will triple by the middle of the twenty-first century. So far, no treatment has prevented or reversed the disease. More than 20 years of multidisciplinary studies have shown that brain zinc dyshomeostasis may play a critical role in AD progression, which provides encouraging clues for metal-targeted therapies in the treatment of AD. Unfortunately, the pilot clinical application of zinc chelator and/or ionophore strategy, such as the use of quinoline-based compounds, namely clioquinol and PBT2, has not yet been successful. The emerging findings revealed a list of key zinc transporters whose mRNA or protein levels were abnormally altered at different stages of AD brains. Furthermore, specifically modulating the expression of some of the zinc transporters in the central nervous system through genetic methods slowed down or prevented AD progression in animal models, resulting in significantly improved cognitive performance, movement, and prolonged lifespan. Although the underlying molecular mechanisms are not yet fully understood, it shed new light on the treatment or prevention of the disease. This review considers recent advances regarding AD, zinc and zinc transporters, recapitulating their relationships in extending our current understanding of the disease amelioration effects of zinc transport proteins as potential therapeutic targets to cure AD, and it may also provide new insights to identify novel therapeutic strategies for ageing and other neurodegenerative diseases, such as Huntington's and Parkinson's disease.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据