Clinical lipidomics: realizing the potential of lipid profilingDysregulation of lipid metabolism plays a major role in the etiology and sequelae of inflammatory disorders, cardiometabolic and neurological diseases, and several forms of cancer. Recent advances in lipidomic methodology allow comprehensive lipidomic profiling of clinically relevant biological samples, enabling researchers to associate lipid species and metabolic pathways with disease onset and progression. The resulting data serve not only to advance our fundamental knowledge of the underlying disease process but also to develop risk assessment models to assist in the diagnosis and management of disease.
Overview of how N32 and N34 elovanoids sustain sight by protecting retinal pigment epithelial cells and photoreceptorsThe essential fatty acid DHA (22:6, omega-3 or n-3) is enriched in and required for the membrane biogenesis and function of photoreceptor cells (PRCs), synapses, mitochondria, etc. of the CNS. PRC DHA becomes an acyl chain at the sn-2 of phosphatidylcholine, amounting to more than 50% of the PRC outer segment phospholipids, where phototransduction takes place. Very long chain PUFAs (n-3, ≥ 28 carbons) are at the sn-1 of this phosphatidylcholine molecular species and interact with rhodopsin. PRC shed their tips (DHA-rich membrane disks) daily, which in turn are phagocytized by the retinal pigment epithelium (RPE), where DHA is recycled back to PRC inner segments to be used for the biogenesis of new photoreceptor membranes.
The role of APOE on lipid homeostasis and inflammation in normal brains: Thematic Review Series: ApoE and Lipid Homeostasis in Alzheimer's DiseaseThe role of APOE in the risk of Alzheimer's disease (AD) has largely focused on its effects on AD pathological processes. However, there are increasing data that APOE genotype affects processes in normal brains. Studies of young cognitively normal humans show effects of APOE genotype on brain structure and activity. Studies of normal APOE knock-in mice show effects of APOE genotype on brain structure, neuronal markers, and behavior. APOE interactions with molecules important for lipid efflux and lipid endocytosis underlie effects of APOE genotype on neuroinflammation and lipoprotein composition.
The ApoE receptors Vldlr and Apoer2 in central nervous system function and disease:The LDL receptor (LDLR) family has long been studied for its role in cholesterol transport and metabolism; however, the identification of ApoE4, an LDLR ligand, as a genetic risk factor for late-onset Alzheimer's disease has focused attention on the role this receptor family plays in the CNS. Surprisingly, it was discovered that two LDLR family members, ApoE receptor 2 (Apoer2) and VLDL receptor (Vldlr), play key roles in brain development and adult synaptic plasticity, primarily by mediating Reelin signaling.