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首页> 外文期刊>Applied biochemistry and biotechnology, Part A. enzyme engineering and biotechnology >Evaluation of the Expression of Amyloid Precursor Protein and the Ratio of Secreted Amyloid Beta 42 to Amyloid Beta 40 in SH-SY5Y Cells Stably Transfected with Wild-Type, Single-Mutant and Double-Mutant Forms of the APP Gene for the Study of Alzheimer's Disease Pathology
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Evaluation of the Expression of Amyloid Precursor Protein and the Ratio of Secreted Amyloid Beta 42 to Amyloid Beta 40 in SH-SY5Y Cells Stably Transfected with Wild-Type, Single-Mutant and Double-Mutant Forms of the APP Gene for the Study of Alzheimer's Disease Pathology

机译：淀粉样蛋白前体蛋白的表达及分泌的淀粉样蛋白β22中的淀粉样蛋白β20与APP基因的野生型细胞中淀粉样蛋白β40与APP基因的双突变形式的淀粉样蛋白β40的比例进行评价，用于研究Alzheimer疾病的研究 病理

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摘要

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.
机译：神经母细胞瘤细胞系如SH-SY5Y是神经变性研究中最常见的模型，其使用在过去几十年中提出了对神经变性病理的理解。在阿尔茨海默病（AD）中，已经描述了几种致病性突变，所有这些突变都会导致升高的病理标志水平，例如淀粉样蛋白β（β）。虽然阿尔茨海默病的遗传学是众所周知的，但家族性广告只占人口中少数病例，其余的是散发性AD，其含有没有已知突变的散发性AD。目前，用于研究AD发病机制的大多数体外模型仅检查β22的水平，作为成功模型生成的确认，并且仅在野生型APP和APP基因的单突变体之间进行比较。最近的发现表明，脑脊液（CSF）中的β42/40比是AD患者的更好诊断指示剂，而不是单独的β22，并且更广泛的β形成，例如intareurogalAβ的积累，β斑块，可溶性低聚Aβ（OAβ）和不溶性原纤维Aβ（FAβ）发生在表达APP的双突变形式（瑞典和印第安纳）的TGCRND8小鼠中，后来导致大脑的逐步损害。在这项研究中，我们生成了与野生型应用程序分开转染的SH-SY5Y细胞，APP的瑞典语突变和APP的瑞典和印第安纳突变，并评估了应用表达以及那些中的β42/40比率细胞。与野生型和单突变细胞相比，APP（瑞典/印第安纳）的APP（瑞典/印第安纳）的应用程序（瑞典/印第安纳）表达了高水平的APP蛋白，并且与野生型和单突变细胞相比，β2/ 40的比例。

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