Food and Nutritional Sciences, Chubu University, Kasugai 487-8501, Japan.
Food and Nutritional Sciences, Chubu University, Kasugai 487-8501, Japan.
Gene. 2021 Feb 5;768:145316. doi: 10.1016/j.gene.2020.145316. Epub 2020 Nov 20.
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.
三磷酸腺苷结合盒转运体（ABC）A7 是一种膜蛋白，属于 ABC 转运体大家族。它与 ABCA1 有 54%的氨基酸残基序列同源，ABC A1 介导细胞磷脂和胆固醇与细胞外螺旋载脂蛋白如载脂蛋白（apo）A-I 从细胞内产生血浆高密度脂蛋白（HDL）。当转染和表达时，ABCA7 也介导 HDL 样颗粒的生成，但颗粒较小，胆固醇含量较低。然而，内源性 ABCA7 不太可能参与 HDL 的生物发生，而是调节宿主防御系统，如细胞的吞噬功能。ABCA1 的表达受细胞胆固醇水平的调节，在肝外周围细胞中由肝 X 受体（LXR）正向调节。然而，在肝脏中它被双重调节，与胆固醇的代谢有关，即 LXR 正向调节，固醇调节元件结合蛋白（SREBP）或肝核因子 4α（HNF4α）负向调节。相比之下，ABCA7 的表达被 SREBP 系统负向调节，因此细胞胆固醇的减少增强了 ABCA7 的功能，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 ABCA7 越来越感兴趣，因为其基因组多样性与晚发性阿尔茨海默病的风险有关。最近的研究结果表明，ABCA7 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来调节 ABCA7 的活性可能为阿尔茨海默病的治疗开辟新途径。
