Membrane lipid therapy: Modulation of the cell membrane composition and structure as a molecular base for drug discovery and new disease treatment. (July 2015)

• Record Type: Journal Article
• Authors: Escribá, Pablo V.; Busquets, Xavier; Inokuchi, Jin-ichi; Balogh, Gábor; Török, Zsolt; Horváth, Ibolya; Harwood, John L.; Vígh, László
• Is Part Of: Progress in lipid research. Volume 59(2015:Jul.)
• Page Start: 38
• Page End: 53
• Publication Date: 2015-07
• Subjects: AA arachidonic acid -- Aβ fibrillar β-amyloid -- ACC acetyl-CoA carboxylase -- Akt protein kinase B -- APP amyloid precursor protein -- ASAH2 neutral ceramidase -- BA benzyl alcohol -- BBB blood–brain-barrier -- BMI body mass index -- BPM bis(monoacylglycero)phosphate -- CALM clathrin assembly lymphoid myeloid domains -- CAMKII calcium/calmodulin-dependent protein kinase II -- Cav1 caveolin 1 -- Cer ceramide -- Chol cholesterol -- CNS central nervous system -- DAG diacylglycerol -- DHA docosahexaenoic acid -- EGFR endothelial growth factor receptor -- ENTH epsin N-terminal homology domains -- EPA eicosapentaenoic acid -- FA fatty acid -- FASN fatty acid synthase gene -- FERM 4.1 protein-ezrin-radixin-moesin -- GEM glycolipid-enriched membrane microdomain -- GLRX glutaredoxin -- GM monosialodihexosylganglioside -- GPCRs G protein-coupled receptors -- GSLs glycosphingolipids -- HA hydroxamic acid -- HSF1 heat shock factor 1 -- Hsp heat shock proteins -- Hsp27 heat shock protein 27 -- Hsp70 heat shock protein 70 -- HSR heat shock response -- INSIG1 insulin-induced gene 1 -- IR insulin receptor -- Ld liquid disordered microdomains -- Lo liquid ordered microdomains -- LDL low density lipoprotein -- LXR liver X receptor -- MAPK mitogen activated protein kinase -- MLT membrane lipid therapy -- MUFA monounsaturated fatty acids -- NMDA N-methyl-d-aspartate -- OLR1 oxidized low-density protein receptor 1 -- PC phosphatidylcholine -- PDGFR platelet derived growth factor receptor -- PDZ domain PSD95-Dlg1-zo-1 domains -- PE phosphatidylethanolamine -- PH domain pleckstrin homology domain -- PHYH phytanoyl CoA dioxygenase -- PIP2 phosphatidylinositol 4, 5-bisphosphate -- PI3K phosphoinositide 3-kinase -- PIP3 phosphatidylinositol (3, 4, 5)-trisphosphate -- PKA protein kinase A -- PKC protein kinase C -- PLA2 phospholipase A2 -- PLC phospholipase C -- PPARs peroxisome proliferator-activated receptors -- PTB domain phosphotyrosine-binding domain -- PUFA polyunsaturated fatty acid -- PYVE domain Fab-1, YGL023, Vps27, and EEA1 domain -- RAR retinoic acid receptor alpha -- REMBRANDT repository for molecular brain neoplasia data -- RXR retinoid X receptor -- S1P sphingosine-1-phosphate -- SCI spinal cord injury -- SGMS1/2 sphingomyelin synthase -- SM sphingomyelin -- SMPD2/3 SM phosphodiesterase 2/3 (neutral sphingomyelinases) -- SNAP23 synaptosomal-associated protein 23 -- SPC sphingosylphosphorylcholine -- SPHK1/2 sphingosine kinase -- SPTLC3 serine palmitoyltransferase -- SREBP1 sterol regulatory element-binding protein 1 -- TAG triacylglycerol -- TCGA cancer genome atlas -- TNF-α tumor necrosis factor alpha -- UGCG ceramide glucosyltransferase -- VLDL very low density lipoprotein; Membrane lipid structure -- Membrane-protein interactions -- Membrane cell signaling -- G protein-membrane interactions -- Membrane-lipid therapy drugs; Lipids -- Periodicals; Lipids -- Periodicals; Lipides -- Périodiques; Lipiden; 572.57
• DOI: 10.1016/j.plipres.2015.04.003
• Languages: English
• ISSNs: 0163-7827

Abstract

Abstract: Nowadays we understand cell membranes not as a simple double lipid layer but as a collection of complex and dynamic protein–lipid structures and microdomains that serve as functional platforms for interacting signaling lipids and proteins. Membrane lipids and lipid structures participate directly as messengers or regulators of signal transduction. In addition, protein–lipid interactions participate in the localization of signaling protein partners to specific membrane microdomains. Thus, lipid alterations change cell signaling that are associated with a variety of diseases including cancer, obesity, neurodegenerative disorders, cardiovascular pathologies, etc. This article reviews the newly emerging field of membrane lipid therapy which involves the pharmacological regulation of membrane lipid composition and structure for the treatment of diseases. Membrane lipid therapy proposes the use of new molecules specifically designed to modify membrane lipid structures and microdomains as pharmaceutical disease-modifying agents by reversing the malfunction or altering the expression of disease-specific protein or lipid signal cascades. Here, we provide an in-depth analysis of this emerging field, especially its molecular bases and its relevance to the development of innovative therapeutic approaches.