期刊
NEUROBIOLOGY OF AGING
卷 51, 期 -, 页码 43-53出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2016.11.001
关键词
Fyn; Alzheimer's disease; SNP; Cerebellum; Hippocampus; Reporter assay
资金
- National Institutes of Health [K99/R00 AG034214, P50 AG05136]
- Jane and Lee Seidman Fund
Neurofibrillary tangles (NFTs), composed of hyperphosphorylated tau, are a key pathologic feature of Alzheimer's disease (AD). Tau phosphorylation is under the control of multiple kinases and phosphatases, including Fyn. Previously, our group found an association between 2 regulatory single nucleotide polymorphisms in the FYN gene with increased tau levels in the cerebrospinal fluid. In this study, we hypothesized that Fyn expression in the brain is influenced by AD status and genetic content. We found that Fyn protein, but not messenger RNA, levels were increased in AD patients compared to cognitively normal controls and are associated with regulatory region single nucleotide polymorphisms. In addition, the expression of the FYN 3'UTR can decrease expression in multiple cell lines, suggesting this regulatory region plays an important role in FYN expression. Taken together, these data suggest that FYN expression is regulated according to AD status and regulatory region haplotype, and genetic variants may be instrumental in the development of neurofibrillary tangles in AD and other tauopathies. (C) 2016 Elsevier Inc. All rights reserved.
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