Sphingolipid Players in Multiple Sclerosis: Their Influence on the Initiation and Course of the Disease

Abstract

Sphingolipids (SLs) play a significant role in the nervous system, as major components of the myelin sheath, contributors to lipid raft formation that organize intracellular processes, as well as active mediators of transport, signaling and the survival of neurons and glial cells. Alterations in SL metabolism and content are observed in the course of central nervous system diseases, including multiple sclerosis (MS). In this review, we summarize the current evidence from studies on SLs (particularly gangliosides), which may shed new light upon processes underlying the MS background. The relevant aspects of these studies include alterations of the SL profile in MS, the role of antibodies against SLs and complexes of SL-ligand-invariant NKT cells in the autoimmune response as the core pathomechanism in MS. The contribution of lipid-raft-associated SLs and SL-laden extracellular vesicles to the disease etiology is also discussed. These findings may have diagnostic implications, with SLs and anti-SL antibodies as potential markers of MS activity and progression. Intriguing prospects of novel therapeutic options in MS are associated with SL potential for myelin repair and neuroprotective effects, which have not been yet addressed by the available treatment strategies. Overall, all these concepts are promising and encourage the further development of SL-based studies in the field of MS.

Effect of Vitamin D Supplementation on Fatigue in Multiple Sclerosis: A Systematic Review and Meta-Analysis

“…Furthermore, there is currently interest in disorders of sphingolipid (SL) metabolism in MS, as they play an important role in the regulation of the immune response and inflammation [ 54 , 55 ]. Recently, fingolimod has been used for the treatment of MS, which is an immunomodulatory drug that targets the sphingosine-1-phosphate receptor and helps reduce inflammation and prevent damage to the myelin sheath [ 56 ].…”

Nutritional roles and therapeutic potentials of dietary sphingomyelin in brain diseases

“…( 33 ) Moreover, current data supports the roles of sphingolipid as players in the MS pathogenesis. ( 34 ) Indeed, Chami et al ( 5 ) analyzed the effects of acid SMase on myelin repair after acute and chronic demyelination and found positive results. Thus, they showed that acid SMase deficient mice had greater myelin recovery and oligodendrocytes count, in addition to lower detrimental astroglial reaction after 2 weeks remyelination in comparison to wild-type animals.…”

Lipids in Psychiatric Disorders: Functional and Potential Diagnostic Role as Blood Biomarkers

“…Myelin is characterized by an extremely high lipid content (~80% of dry weight) and a peculiar lipid composition in which the ratio of cholesterol to phospholipids (mainly ethanolamine phosphatide and phosphatidylcholine) to glycolipids (e.g., galactosylceramide and sulfatide) is approximately 2:2:1. Specific SPs and glycerides are substances that cover nerve fibers and accelerate the transmission of nerve impulses [11]. Myelin is particularly high in saturated and monounsaturated lower and higher fatty acids.…”