期刊
APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY
卷 183, 期 3, 页码 853-866出版社
HUMANA PRESS INC
DOI: 10.1007/s12010-017-2468-6
关键词
Stable transfection; Amyloid precursor protein; Amyloid-beta; Alzheimer's disease; Swedish mutation; Swedish/Indiana mutation
资金
- Universiti Kebangsaan Malaysia [DIP/2013/003, FF-2015-025]
- Ministry of Higher Education [LRGS/BU/2012/UKM-UKM/K/04]
Neuroblastoma cell lines such as SH-SY5Y are the most frequently utilized models in neurodegenerative research, and their use has advanced the understanding of the pathology of neurodegeneration over the past few decades. In Alzheimer's disease (AD), several pathogenic mutations have been described, all of which cause elevated levels of pathological hallmarks such as amyloid-beta (A beta). Although the genetics of Alzheimer's disease is well known, familial AD only accounts for a small number of cases in the population, with the rest being sporadic AD, which contains no known mutations. Currently, most of the in vitro models used to study AD pathogenesis only examine the level of A beta 42 as a confirmation of successful model generation and only perform comparisons between wild-type APP and single mutants of the APP gene. Recent findings have shown that the A beta 42/40 ratio in cerebrospinal fluid (CSF) is a better diagnostic indicator for AD patients than is A beta 42 alone and that more extensive A beta formation, such as accumulation of intraneuronal A beta, A beta plaques, soluble oligomeric A beta (oA beta), and insoluble fibrillar A beta (fA beta) occurs in TgCRND8 mice expressing a double-mutant form (Swedish and Indiana) of APP, later leading to greater progressive impairment of the brain. In this study, we generated SH-SY5Y cells stably transfected separately with wild-type APP, the Swedish mutation of APP, and the Swedish and Indiana mutations of APP and evaluated the APP expression as well as the A beta 42/40 ratio in those cells. The double-mutant form of APP (Swedish/Indiana) expressed markedly high levels of APP protein and showed a high A beta 2/40 ratio compared to wild-type and single-mutant cells.
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