作者
Bess Frost, Martin Hemberg, Jada Lewis, Mel B Feany
发表日期
2014/3
期刊
Nature neuroscience
卷号
17
期号
3
页码范围
357-366
出版商
Nature Publishing Group US
简介
The microtubule-associated protein tau is involved in a number of neurodegenerative disorders, including Alzheimer's disease. Previous studies have linked oxidative stress and subsequent DNA damage to neuronal death in Alzheimer's disease and related tauopathies. Given that DNA damage can substantially alter chromatin structure, we examined epigenetic changes in tau-induced neurodegeneration. We found widespread loss of heterochromatin in tau transgenic Drosophila and mice and in human Alzheimer's disease. Notably, genetic rescue of tau-induced heterochromatin loss substantially reduced neurodegeneration in Drosophila. We identified oxidative stress and subsequent DNA damage as a mechanistic link between transgenic tau expression and heterochromatin relaxation, and found that heterochromatin loss permitted aberrant gene expression in tauopathies. Furthermore, large-scale analyses …
学术搜索中的文章
B Frost, M Hemberg, J Lewis, MB Feany - Nature neuroscience, 2014