Sphingolipids as prognostic biomarkers of neurodegeneration, neuroinflammation, and psychiatric diseases and their emerging role in lipidomic investigation methods

Abstract

Lipids play an important role in neurodegeneration, neuroinflammation, and psychiatric disorders and an imbalance in sphingolipid levels is associated with disease. Although early diagnosis and intervention of these disorders would clearly have favorable long-term outcomes, no diagnostic tests currently exist that can accurately identify people at risk. Reliable prognostic biomarkers that are easily accessible would be beneficial to determine therapy and treatment response in clinical trials. Recent advances in lipidomic investigation methods have greatly progressed the knowledge of sphingolipids in neurodegenerative and psychiatric disorders over the past decades although more longitudinal studies are needed to understand its exact role in these disorders to be used as potential tools in the clinic. In this review, we give an overview of the current knowledge of sphingolipids in neurodegenerative and psychiatric disorders and explore recent advances in investigation methods. Finally, the potential of sphingolipid metabolism products and signaling molecules as potential biomarkers for diagnosis, prognostic, or surrogate markers of treatment response is discussed.

New Insights into Multiple Sclerosis Mechanisms: Lipids on the Track to Control Inflammation and Neurodegeneration

“…They play an important role in organization and compartmentalization of the membrane into so-called microdomains or lipid rafts. These are involved in the processes of exo- and endocytosis, cell polarity, and intracellular signaling, as well as activation of ion channels and binding ligands to receptors [ 21 , 22 ]. Moreover, changes in intracellular SL levels are responsible for the dynamic balance between cell viability and destruction.…”

“…Proper integrity and organization of neuronal membranes, provided by their lipid components, is essential for processes of neuronal polarization and differentiation, formation of synapses and interaction between neurons and glial cells, and activity and plasticity of neuronal networks. Therefore, regulation of the SL signaling network is crucial for proper function of CNS, and its disturbances were demonstrated to be involved in the background of a range of neuroinflammatory and neurodegenerative diseases [ 21 , 22 , 23 ]. SLs exert pronounced effects on inflammation in the context of autoimmunity, acting either as targets and also modulators of the immune response, with myelin sheath reported to induce apoptosis in auto-reactive T cells [ 24 ] and to ameliorate EAE [ 25 , 26 ].…”

An imaging mass spectrometry atlas of lipids in the human neurologically normal and Huntington’s disease caudate nucleus

“…Indeed, the sphingosine 1‐phosphate receptor modulator fingolimod is an approved therapy for the latter indication (van Kruining et al. 2020; Matloubian et al. 2004).…”

“…Alterations in sphingolipid species are increasingly reported in the context of neurodegenerative diseases such as multiple sclerosis. Indeed, the sphingosine 1-phosphate receptor modulator fingolimod is an approved therapy for the latter indication (van Kruining et al 2020;Matloubian et al 2004).…”

Retention dependences support highly confident identification of lipid species in human plasma by reversed-phase UHPLC/MS

“…Lipidomics is aimed to understand the function of lipids in biological systems. Dysregulated lipids have been reported for various serious diseases, such as diabetes mellitus [2], cancer [3], cardiovascular diseases [4,5], obesity [6], neurodegenerative disorders [7], etc. [8][9][10].…”