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

在过去的十年里，我们的团队已经记录了一种优雅的机制，通过这种机制，受伤的成人大脑使用死亡或垂死细胞释放的胆固醇和磷脂来喂养存活的神经元，这些神经元正在重建新的突触网络，试图减轻丢失或受损的输入。细胞研究表明，细胞内产生的胆固醇是通过一系列称为atp结合盒（ABC）复合物来运输的。ABC转运蛋白是一种膜蛋白，可在细胞内和跨膜运输多种底物。特别是ABCA和ABCG亚类参与磷脂和/或胆固醇在质膜上的转运，其中一些基因的突变与脂质和固醇稳态失调有关。由于ABCA1和ABCG1都在脑中表达，因此CNS中脂蛋白数量的一个关键决定因素可能是apoE（由胶质细胞合成）和apoAI（来自血浆）的脂化，这两种转运蛋白由一种或两种转运蛋白介导。

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.