Role of apolipoproteins and ABC transporters during brain reinnervation in the adult mice

在过去的十年里，我们的团队记录了一种优雅的机制，通过这种机制，受损的成年大脑使用死亡或濒临死亡的细胞释放的胆固醇和磷脂来喂养正在重建新突触网络的存活神经元，试图减轻丢失或损坏的输入。细胞研究表明，细胞内产生的胆固醇是由一系列被称为三磷酸腺苷结合盒(ABC)复合体运输的。ABC转运蛋白是一种膜蛋白，可以在细胞内和跨膜运输各种底物。ABCA和ABCG亚类尤其参与磷脂和/或胆固醇通过质膜的运输，其中几个基因的突变与调节失调的脂质和类固醇稳态有关。由于ABCA1和Abcg1都在脑中表达，中枢神经系统脂蛋白群体的一个关键决定因素可能是这两个转运蛋白中的一个或两个介导的apoE(由胶质细胞合成)和apoAI(来自血浆)的脂化。

Over the past ten years, our team has documented an elegant mechanism by which the injured adult brain uses the cholesterol and phospholipids released from dead or dying cells to feed surviving neurons which are in the process of rebuilding new synaptic networks, in an attempt to alleviate the lost or damaged inputs. Cell studies have shown that the cholesterol produced intracellularly is transported by a series of complexes called the ATP-Binding Cassette (ABC) complexes. The ABC transporters are membrane proteins that transport a wide variety of substrates intracellularly and across membranes. The ABCA and ABCG subclasses in particular are involved in the transport of phospholipids and/or cholesterol across the plasma membrane, and mutations in several of these genes are associated with dysregulated lipid and sterol homeostasis. Because both ABCA1 and ABCG1 are expressed in brain, a key determinant of the lipoprotein population in CNS is likely to be the lipidation of apoE (synthesized by glia) and apoAI (derived from plasma) mediated by one or both of these transporters.