ABCA7 links sterol metabolism to the host defense system: Molecular background for potential management measure of Alzheimer's disease.
ABCA7 links sterol metabolism to the host defense system: Molecular background for potential management measure of Alzheimer's disease.
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ABCA7将类固醇代谢与宿主防御系统联系起来：阿尔茨海默病潜在管理措施的分子背景。
DOI：
10.1016/j.gene.2020.145316
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发表时间：
2021-02-05
期刊：
影响因子：
3.5
通讯作者：
Yokoyama S
中科院分区：
文献类型：
--
作者：
Abe-Dohmae S;Yokoyama S
ATP结合盒转运蛋白（ABC）A7是一种膜蛋白，属于ABC转运蛋白大家族。其氨基酸残基序列与ABCA 1具有54%的同源性，ABCA 1介导血浆高密度脂蛋白（HDL）从细胞磷脂和胆固醇与细胞外螺旋载脂蛋白（apo）A-I的生物合成。当转染和表达时，ABCA 7也介导HDL样颗粒的产生，但小且胆固醇含量较少。然而，内源性ABCA 7不太可能参与HDL生物合成，而是调节宿主防御系统，如细胞的吞噬功能。ABCA 1的表达受细胞胆固醇水平的调节，并受肝外外周细胞中的肝X受体（LXR）的调节。然而，它在肝脏中受到双重调节，与胆固醇的转运有关，用于其催化剂; LXR为阳性，固醇调节元件结合蛋白（SREBP）或肝核因子4α（HNF 4 α）为阴性。相反，ABCA 7的表达被显示为受到SREBP系统的负调控，因此细胞胆固醇的降低增强了ABCA 7的功能，例如细胞吞噬反应，这表明它将胆固醇代谢与宿主防御系统联系起来。人们对ABCA 7的兴趣正在增加，因为已经发现其基因组多样性与迟发性阿尔茨海默病的风险有关。最近的研究表明ABCA 7参与淀粉样β肽的代谢，包括其吞噬清除。因此，通过操纵胆固醇代谢调节ABCA 7活性可能为阿尔茨海默病的管理开辟新的途径。
ATP-binding cassette transporter (ABC) A7 is a membrane protein that belongs to the large family of ABC transporters. It is 54% homologous in amino acid residue sequence to ABCA1 which mediates biogenesis of plasma high density lipoprotein (HDL) from cellular phospholipid and cholesterol with extracellular helical apolipoproteins such as apolipoprotein (apo) A-I. When transfected and expressed, ABCA7 also mediates generation of HDL-like particles but small and of less cholesterol content. However, endogenous ABCA7 is unlikely involved in HDL biogenesis and rather to regulate the host-defense system such as phagocytotic function of the cells. ABCA1 expression is regulated by cellular cholesterol levels, positively by the liver X receptor (LXR) in extrahepatic peripheral cells. However, it is modulated dually in the liver being relevant to transport of cholesterol for its catabolism; positively by LXR and negatively by sterol regulatory element binding protein (SREBP) or hepatic nuclear factor 4α (HNF4α). In contrast, ABCA7 expression was shown to be regulated negatively by the SREBP system so that decrease of cell cholesterol enhances ABCA7 function such as cellular phagocytotic reaction, suggesting that it links cholesterol metabolism to the host defense system. The interest is being build up in ABCA7 as its genomic diversity has been found related to a risk for late-onset Alzheimer’s diseases. More recent findings indicate that ABCA7 is involved in metabolism of amyloid β peptide including its phagocytotic clearance. Accordingly, modulation of ABCA7 activity by manipulating cholesterol metabolism may open a new path for management of Alzheimer’s disease.
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影响因子：
6.5
作者：
Abe-Dohmae, Sumiko;Kato, Koichi H.;Yokoyama, Shinji
通讯作者：
Yokoyama, Shinji
影响因子：
4.8
作者：
Kim, WS;Fitzgerald, ML;Freeman, MW
通讯作者：
Freeman, MW
影响因子：
30.8
作者：
Bodzioch, M;Orsó, E;Schmitz, G
通讯作者：
Schmitz, G
影响因子：
4.8
作者：
Arakawa, R;Yokoyama, S
通讯作者：
Yokoyama, S
DOI：
10.1006/bbrc.2000.3880
发表时间：
2000-11-30
影响因子：
3.1
作者：
Kaminski, WE;Piehler, A;Schmitz, G
通讯作者：
Schmitz, G