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

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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.