Sphingolipids in Multiple Sclerosis

Abstract

Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the CNS. Oligodendrocytes, the myelin forming cells of the central nervous system (CNS), are target cells in MS. Although the etiology of MS is poorly known, new insights suggest oligodendrocyte apoptosis as one of the critical events followed by glial activation and infiltration of lymphocytes and macrophages. A major breakthrough in delineation of the mechanism of cell death, perivascular cuffing and glial activation came from elucidation of the sphingolipid signal transduction pathway. The sphingolipid signal transduction pathway induces apoptosis, differentiation, proliferation, and growth arrest depending upon cell and receptor types, and downstream targets. Sphingomyelin, a major component of myelin membrane formed by mature oligodendrocytes, is abundant in the CNS and ceramide, its primary catabolic product released by activation of either neutral or acidic sphingomyelinase, serves as a potential lipid second messenger or mediator molecule modulating diverse cellular signaling pathways. Similarly, under certain conditions, sphingosine produced from ceramide by ceramidase is phosphorylated by sphingosine kinases to sphingosine-1 phosphate, another potent second messenger molecule. Both ceramide and sphingosine-1 phosphate regulate life and death of many cell types including brain cells and participate in pathogenic processes of MS. In this review, we have made an honest attempt to compile recent findings made by others and us relating to the role of sphingolipids in the disease process of MS.

Application of Raman spectroscopy for visualizing biochemical changes during peripheral nerve injuryin vitroandin vivo

“…The bands at 2853 and 2885 cm −1 are derived from lipids, 21,22 and peripheral nerve tissue is rich in lipids in myelin sheaths that surround axons to support neural electrical activity. [28][29][30][31] Myelin is supplied by Schwann cells and myelin lipids include sphingomyelin and the glycolipid galactocerebroside. Schwann cells had similar spectral patterns at 2851 and 2885 cm −1 and Raman spectra of sphingomyelin showed similar patterns to that of Schwann cells.…”

Novel Insights into Acid-Sensing Ion Channels: Implications for Degenerative Diseases

“…Although the etiology of MS is unclear, new insights suggest oligodendrocyte apoptosis as one of the critical events in physiological and pathophysiological processes [41]. Several studies have revealed that cytokine and ionic imbalance are the most important factors in axonal degeneration through inducing neuron mitochondrial dysfunction, alteration of ion exchange mechanisms and energy failure [42].…”

Identification of early gene expression changes during human Th17 cell differentiation

“…The role of the T-cell sphingolipid metabolism on the Th17 differentiation or function has not been explored. Interestingly though, altered sphingolipid metabolism is associated with pathogenesis of multiple sclerosis, 44 and externally added sphingolipids augment Th17 differentiation. 45 We also validated the Th17 cell-associated up-regulation of long noncoding RNA MIAT, mRNA of structural protein COL6A3 encoding ␣-3 chain of the type VI collagen, and LMNA which is one of the nuclear lamina proteins.…”