Bioactive Sphingolipids in Health and Disease

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About this Research Topic

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Background

Experimental and clinical studies have revealed the function of sphingolipids in the pathogenesis of diseases/conditions such as hypertension, diabetes mellitus, coronary artery disease, and stroke. They are involved in the regulation of numerous cellular processes. Ceramides (CERs) serve as precursors for sphingomyelins (SMs) and are bioactive hydrophobic backbones of SMs. Ceramide can be generated through de novo synthesis, hydrolysis of sphingomyelin by sphingomyelinase (SMase), and breakdown of glycosphingolipids. The de novo synthesis of CER occurs in the endoplasmic reticulum and in mitochondrial membranes. The formation of CERs also leads to the production of metabolites such as ceramide-1-phosphate (C1P), sphingosine, and sphingosine-1-phosphate (S1P) which are key regulators of inflammation. Both S1P and C1P stimulate cell proliferation and inhibit apoptosis.

Biologically active sphingolipids have important roles in the operation of several vital biological functions. The latest considerable advances in the knowledge of biologically active sphingolipid synthesis, particularly within ceramide and S1P-mediated pathways, have identified central roles for these molecules both in cancer and type II diabetes. Ceramide, a chief molecule in sphingolipid metabolism, functions as a tumor-suppressor lipid, triggering antiproliferative and apoptotic reactions in various cancer cells. Quite the reverse, S1P and C1P induces responses that combined, make S1P and C1P a tumor-promoting lipid. Plasma ceramides are elevated in obese type II diabetes patients and the increase correlates with the degree of insulin resistance and inflammation. These findings are paving the way for the progression of new therapies associated with the pathogenesis of inflammation-associated illnesses such as atherosclerosis, type II diabetes, obesity, and cancer.

Sphingolipids are ubiquitous lipids that have excessive functions from the arrangement of structural domains to cellular trafficking and signal transduction. Recent research described many of the crucial enzymes implicated in sphingolipid metabolism and this has guided new therapeutic strategies against inflammation-associated illnesses such as atherosclerosis, type II diabetes, obesity, and cancer. The scope of the research topic includes major pathways in sphingolipid metabolism and discusses these in relation to disease and therapy.

• Sphingolipids in Cell Cycle

• Sphingolipids in Cell Growth and Proliferation

• Sphingolipids in Cell Migration

• Sphingolipids in Immunology

• Sphingolipids in Inflammation

• Sphingolipids in Metabolism

Keywords: Sphingolipid, Health, Disease, Function, Immunology, Metabolism

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