期刊
FRONTIERS IN MOLECULAR NEUROSCIENCE
卷 13, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fnmol.2020.572308
关键词
copper; tau; aggregation; oxidative stress; Alzheimer's disease
资金
- Croatian Science Foundation (Hrvatska Zaklada za Znanost) [IP-2019-04-3584]
- Scientific Centre of Excellence for Basic, Clinical, and Translational Neuroscience CORE-NEURO (Experimental and clinical research of hypoxic-ischemic damage in perinatal and adult brain - European Union through the European Regional Development Fund) [GA KK01.1.1.01.0007]
- National Institutes of Health (NIH) [AG005138, AG066514]
All tauopathies, including Alzheimer's disease (AD), are characterized by the intracellular accumulation of abnormal forms of tau protein in neurons and glial cells, which negatively affect microtubule stability. Under physiological conditions, tubulin-associated unit (Tau) protein is intrinsically disordered, almost without secondary structure, and is not prone to aggregation. In AD, it assembles, and forms paired helical filaments (PHFs) that further build-up neurofibrillary tangles (NFTs). Aggregates are composed of hyperphosphorylated tau protein that is more prone to aggregation. The pathology of AD is also linked to disturbed copper homeostasis, which promotes oxidative stress (OS). Copper imbalance is widely observed in AD patients. Deregulated copper ions may initiate and exacerbate tau hyperphosphorylation and formation of beta-sheet-rich tau fibrils that ultimately contribute to synaptic failure, neuronal death, and cognitive decline observed in AD patients. The present review summarizes factors affecting the process of tau aggregation, conformational changes of small peptide sequences in the microtubule-binding domain required for these motifs to act as seeding sites in aggregation, and the role of copper in OS induction, tau hyperphosphorylation and tau assembly. A better understanding of the various factors that affect tau aggregation under OS conditions may reveal new targets and novel pharmacological approaches for the therapy of AD.
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