About this Research Topic
The post genomic/proteomic era is marked by interests in understanding molecular changes in the central nervous system (CNS) that may be critical to related disorders. Lipids are becoming a major focus of research because of the critical role that they play in the structure and function of the CNS. Thus, the aim of this topic is to examine how lipid metabolism and transport influence CNS health and disease.
The CNS lipodome is made up of several major classes of lipids. As with all lipidomes, fatty acyls are the major building blocks. The major fatty acyl components include saturated (SAFAs), monounsaturated (MUFA), and polyunsaturated fatty acids (PUFA). The relative composition of CNS membranes dictates the structure and function of cellular components. For example, cellular lipids enriched with SAFAs are more likely to generate neurotoxic amyloid peptides due to the dysfunctional metabolism of amyloid precursor proteins. In contrast, MUFAs are neurotrophic factors that support brain health, while PUFAs are susceptible to oxidative damage and are precursors of pain and inflammation.
The other classes of CNS lipids include glycerolipids, glycerophospholipids, sphingolipids, sterol lipids, and isoprenoid-derived lipids such as CoQ10. A unique combination of these lipids is necessary for generating functional components of the CNS such as the blood brain barrier (BBB) and myelin sheaths.
Lipoproteins are complex particles that enable the transport of phospholipids and cholesterol between glia and neurons in the CNS, and thus are important for a number of essential CNS functions. High–density lipoproteins (HDL) are mostly found in the CNS and contain distinct apoprotein isoforms (e.g ApoA1, ApoJ, and ApoE). Unsurprisingly, several GWAS studies have associated certain lipoproteins with brain disorders. For example, the ApoE e4 allele is a major genetic risk factor for sporadic late onset AD, stroke, and other CNS disorders. Thus, an understanding of how CNS lipoproteins change with brain development, aging, and other CNS disorders is highly warranted, and likely to reveal novel mechanisms and highlight new therapeutic interventions.
Growing evidence now suggests that the CNS lipidome changes during development and is altered in disease. Therefore, it is of paramount importance to comprehensively examine lipid metabolism in the CNS to facilitate the discovery of disease mechanisms, novel biomarkers, and new strategies to treat disabling disorders such as Alzheimer’s disease, migraine, stroke, and other cognitive disorders.
The contributions in this Research Topic will help to define the composition of lipids and lipoproteins in CNS health. We will also examine known functions of CNS lipids/lipoproteins (in terms of structural, signaling, inflammation, oxidation, and immune functions) that underlie their contributions to CNS disorders. We expect that this comprehensive examination of lipid and lipoprotein metabolism will result in a better understanding of CNS physiology and will identify novel disease modifiers that may lead to improved diagnosis and new therapies.
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