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

载脂蛋白和 ABC 转运蛋白在成年小鼠大脑神经支配中的作用

• 批准号: 355917-2009
• 负责人: Poirier, Judes
• 金额: $ 1.82万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2010
• 资助国家: 加拿大
• 起止时间: 2010-01-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=459641
• 关键词: Role; apolipoproteins; ABC; transporters; during

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.

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，受伤的成年大脑使用死亡或垂死细胞释放的胆固醇和磷脂来喂养幸存的神经元，这些神经元正在重建新的突触网络，试图减轻丢失或损坏的输入。细胞研究表明，细胞内产生的胆固醇通过一系列称为ATP结合盒（ABC）复合物的复合物转运。ABC转运蛋白是在细胞内和跨膜转运多种底物的膜蛋白。特别是ABCA和ABCG亚类参与磷脂和/或胆固醇跨质膜的转运，并且这些基因中的几个中的突变与脂质和固醇稳态失调相关。由于ABCA 1和ABCG 1均在脑中表达，因此CNS中脂蛋白群体的关键决定因素可能是由这些转运蛋白中的一种或两种介导的apoE（由神经胶质合成）和apoAI（来源于血浆）的脂化。