Role of ATP-binding cassette transporters in brain lipid transport and neurological disease.
The brain is lipid-rich compared to other organs and although previous studies have highlighted the importance of ATP-binding cassette (ABC) transporters in the regulation of lipid transport across membranes in peripheral tissues, very little is known regarding ABC transporter function in the CNS. In this study, we bring together recent literature focusing on potential roles for ABC transporters in brain lipid transport and, where appropriate, identify possible links between ABC transporters, lipid transport and neurological disease. Of the 48 transcriptionally active ABC transporters in the human genome, we have focused on 13 transporters (ABCA1, ABCA2, ABCA3, ABCA4, ABCA7 and ABCA8; ABCB1 and ABCB4; ABCD1 and ABCD2; ABCG1, ABCG2, and ABCG4) for which there is evidence suggesting they may contribute in some way to brain lipid transport or homeostasis. The transporters are discussed in terms of their location within brain regions and brain cell types and, where possible, in terms of their known functions and established or proposed association with human neurological diseases. Specific examples of novel treatment strategies for diseases, such as Alzheimer's disease and X-linked adrenoleukodystrophy that are based on modulation of ABC transporter function are discussed and we also examine possible functions for specific ABC transporters in human brain development.
Kim
Woojin Scott
WS
Prince of Wales Medical Research Institute, Sydney, New South Wales, Australia.
Weickert
Cynthia Shannon
CS
Garner
Brett
B
D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001693:Biological Transport, Active / Q000235:genetics / Q000502:physiology; D001921:Brain / Q000378:metabolism*; D006706:Homeostasis / Q000235:genetics / Q000502:physiology; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics / Q000502:physiology*; D009422:Nervous System Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
D018528:ATP-Binding Cassette Transporters