Sphingolipids in neuroinflammation: a potential target for diagnosis and therapy

Abstract

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]

Alteration in the Cerebrospinal Fluid Lipidome in Parkinson’s Disease: A Post-Mortem Pilot Study

“…Chronic neuroinflammation is a landmark of PD [ 64 ]. Sphingolipids, significantly increased in our study, have been recently proposed as potential diagnostic and therapeutic targets in PD, due to their direct involvement in neuroinflammation [ 65 ]. They are particularly relevant in immune-cell trafficking, cytokine signaling, production of pro-inflammatory eicosanoids and the regulation of cellular mechanisms involved in multiple inflammatory processes [ 66 , 67 ].…”

Sphingolipids and Diagnosis, Prognosis, and Organ Damage in Systemic Lupus Erythematosus

“…In addition, studies have shown that sphingolipids play a significant role in the pathogenesis of several neuroinflammatory disorders such as Alzheimer's disease and Parkinson's disease (68,69). During early phases of neuroinflammation, astrocytic sphingolipid alterations, which include an increase in ceramide and decrease in SKs that generate S1P were reported (68,70). More information regarding the role of sphingolipids in neuroinflammation were reviewed previously (68,69,71).…”

“…During early phases of neuroinflammation, astrocytic sphingolipid alterations, which include an increase in ceramide and decrease in SKs that generate S1P were reported (68,70). More information regarding the role of sphingolipids in neuroinflammation were reviewed previously (68,69,71).…”

Sphingolipids and Cell Signaling: Relationship Between Health and Disease in the Central Nervous System

“…Finally, in microglia different sphingolipids patterns can be observed according to its activation stage. In this aspect, proinflammatory roles have been associated with long-chain ceramides (C16-C24) and S1P, whereas short-chain ceramides exert antiinflammatory effects in the CNS [53][54][55]. Complex sphingolipids are present in neuron's axon plasma membrane, which interact with the myelin-associated glycoprotein (MAG), contributing to the myelin stabilization.…”