Sphingolipid Catabolism and Glycerophospholipid Levels Are Altered in Erythrocytes and Plasma from Multiple Sclerosis Patients

Abstract

Multiple sclerosis (MS) is an autoimmune, inflammatory, degenerative disease of the central nervous system. Changes in lipid metabolism have been suggested to play important roles in MS pathophysiology and progression. In this work we analyzed the lipid composition and sphingolipid-catabolizing enzymes in erythrocytes and plasma from MS patients and healthy controls. We observed reduction of sphingomyelin (SM) and elevation of its products—ceramide (CER) and shingosine (SPH). These changes were supported by the detected up-regulation of the activity of acid sphingomyelinase (ASM) in MS plasma and alkaline ceramidase (ALCER) in erythrocytes from MS patients. In addition, Western blot analysis showed elevated expression of ASM, but not of ALCER. We also compared the ratios between saturated (SAT), unsaturated (UNSAT) and polyunsaturated fatty acids and suggest, based on the significant differences observed for this ratio, that the UNSAT/SAT values could serve as a marker distinguishing erythrocytes and plasma of MS from controls. In conclusion, the application of lipid analysis in the medical practice would contribute to definition of more precise diagnosis, analysis of disease progression, and evaluation of therapeutic strategies. Based on the molecular changes of blood lipids in neurodegenerative pathologies, including MS, clinical lipidomic analytical approaches could become a promising contemporary tool for personalized medicine.

Experimental Analysis of Tear Fluid and Its Processing for the Diagnosis of Multiple Sclerosis

“…Together with glycerophospholipids, sphingolipids are essential for numerous cellular processes, such as cell division, signaling processes, apoptosis, and engagement in pro-or anti-proliferative pathways. Sphingolipids are involved in the etiology of MS and are highly expressed in the central nervous system [60].…”

Therapeutic Plasma Exchange and Multiple Sclerosis Dysregulations: Focus on the Removal of Pathogenic Circulatory Factors and Altering Nerve Growth Factor and Sphingosine-1-Phosphate Plasma Levels

“…S1P can also be reversibly dephosphorylated by S1P phosphatase to produce sphingosine, the levels of which are generally controlled by flux through de novo ceramide synthesis and sphingosine catabolic pathways [126]. There are numerous studies on the sphingomyelin (SM)-S1P pathway in order to reveal whether SM serves as a major source of S1P through the activities of sphingolipid metabolizing enzymes [127]. The obtained results showed upregulation of certain sphingolipid catabolizing enzymes, implying that SM could serve as a possible source of S1P (Figure 6).…”

Repurposing of multiple sclerosis (MS) and graft versus host disease (GVHD) therapeutics to inhibit chronic rejection of transplanted organs

“…Fingolimod (Gilenya, FTY720) is a derivative of fungal metabolite myriocin, which structure resembles sphingosine (15,16). Fingolimod (Gilenya, FTY720) and its familial compound siponimod (Mayzent) are used for the treatment of multiple sclerosis (MS) [17,18].…”