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, 53 (1), 28-34

Sphingolipids in Neuroinflammation: A Potential Target for Diagnosis and Therapy


Sphingolipids in Neuroinflammation: A Potential Target for Diagnosis and Therapy

Ju Youn Lee et al. BMB Rep.


Sphingolipids are ubiquitous building blocks of eukaryotic cell membranes that function as signaling molecules for regulating a diverse range of cellular processes, including cell proliferation, growth, survival, immune-cell trafficking, vascular and epithelial integrity, and inflammation. Recently, several studies have highlighted the pivotal role of sphingolipids in neuroinflammatory regulation. Sphingolipids have multiple functions, including induction of the expression of various inflammatory mediators and regulation of neuroinflammation by directly effecting the cells of the central nervous system. Accumulating evidence points to sphingolipid engagement in neuroinflammatory disorders, including Alzheimer's and Parkinson's diseases. Abnormal sphingolipid alterations, which involves an increase in ceramide and a decrease in sphingosine kinase, are observed during neuroinflammatory disease. These trends are observed early during disease development, and thus highlight the potential of sphingolipids as a new therapeutic and diagnostic target for neuroinflammatory diseases. [BMB Reports 2020; 53(1): 28-34].

Conflict of interest statement


The authors have no conflicting interests.


Fig. 1
Fig. 1
Sphingolipid metabolism and interconnected bioactive sphingolipid metabolites. The various enzymes that mediate interconversion between various bioactive lipids are localized with the lipids themselves. Ceramide is produced from sphingomyelin by SMase. Ceramide can be hydrolyzed to sphingosine, which is then phosphorylated to sphingosine-1-phosphate (S1P) by sphingosine kinase (SphK).
Fig. 2
Fig. 2
The role of neuronal SphK1 in neuroinflammation. (A) Left, the role of SphK1 as an ATP-dependent lipid kinase that catalyzes the conversion of sphingosine to S1P, which in turn generates cellular responses including proliferation, angiogenesis, and migration. Right, the novel role of SphK1 as an acetyl-CoA dependent acetyltransferase with activity directed toward COX2, using sphingosine as the substrate. These enzyme activities induce SPM secretion, resulting in the resolution of neuroinflammation. (B) In neuroinflammatory environments, including those with the presence of Aβ, neuronal SphK1 decreases, which impairs S565 acetylation of COX2 and reduces SPMs secretion. Decreased SPM secretion in neurons reduced the number of microglia with a phagocytic phenotype.
Fig. 3
Fig. 3
Changes in bioactive sphingolipid levels observed during neuroinflammation. Numerous observations in neuroinflammatory environments demonstrate changes in sphingolipid levels. Ceramide is increased in the neurons and glial cells of neuroinflammatory environments. S1P expressed by SphK1 is elevated in the neuroinflammatory environments of glial cells. Neuronal SphK is reduced, regardless of S1P alternations.

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