Sphingosine kinase and sphingosine-1-phosphate: regulators in autoimmune and inflammatory disease

Snider, Ashley J.

doi:10.2217/ijr.13.40

Cited by 29 publications

(19 citation statements)

References 87 publications

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“…Therefore, due to their clinical heterogeneity, affecting potentially any organ of the body such as renal involvement may advise future neurological therapeutic perspectives. In that regard, studies have shown elevated S1P serum levels in patients with juvenile onset SLE [196] as well as in MRL-lpr/lpr mice [197]. In light of therapeutic targets for SLE, previous studies have concentrated on lupus nephritis.…”

Section: The Sphingolipid Metabolism In Neuroinflammatory Disordersmentioning

confidence: 99%

The S1P–S1PR Axis in Neurological Disorders—Insights into Current and Future Therapeutic Perspectives

Lucaciu

Brunkhorst

Pfeilschifter

et al. 2020

Cells

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Sphingosine 1-phosphate (S1P), derived from membrane sphingolipids, is a pleiotropic bioactive lipid mediator capable of evoking complex immune phenomena. Studies have highlighted its importance regarding intracellular signaling cascades as well as membrane-bound S1P receptor (S1PR) engagement in various clinical conditions. In neurological disorders, the S1P–S1PR axis is acknowledged in neurodegenerative, neuroinflammatory, and cerebrovascular disorders. Modulators of S1P signaling have enabled an immense insight into fundamental pathological pathways, which were pivotal in identifying and improving the treatment of human diseases. However, its intricate molecular signaling pathways initiated upon receptor ligation are still poorly elucidated. In this review, the authors highlight the current evidence for S1P signaling in neurodegenerative and neuroinflammatory disorders as well as stroke and present an array of drugs targeting the S1P signaling pathway, which are being tested in clinical trials. Further insights on how the S1P–S1PR axis orchestrates disease initiation, progression, and recovery may hold a remarkable potential regarding therapeutic options in these neurological disorders.

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Section: The Sphingolipid Metabolism In Neuroinflammatory Disordersmentioning

confidence: 99%

The S1P–S1PR Axis in Neurological Disorders—Insights into Current and Future Therapeutic Perspectives

Lucaciu

Brunkhorst

Pfeilschifter

et al. 2020

Cells

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“…Phosphorylation of sphingosine is catalyzed by sphingosine kinase (SK) (Heffernan-Stroud and Obeid 2013; Lima and Spiegel 2013; Pitson 2011; Pyne et al 2012; Siow et al 2011; Snider 2013; Wattenberg 2010). There are two sphingosine kinases, namely SK1 and SK2.…”

Section: Sphingolipid Metabolismmentioning

confidence: 99%

Sphingolipids and mitochondrial apoptosis

Patwardhan

Beverly

Siskind

2015

J Bioenerg Biomembr

109

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The sphingolipid family of lipids modulate several cellular processes, including proliferation, cell cycle regulation, inflammatory signaling pathways, and cell death. Several members of the sphingolipid pathway have opposing functions and thus imbalances in sphingolipid metabolism result in deregulated cellular processes, which cause or contribute to diseases and disorders in humans. A key cellular process regulated by sphingolipids is apoptosis, or programmed cell death. Sphingolipids play an important role in both extrinsic and intrinsic apoptotic pathways depending on the stimuli, cell type and cellular response to the stress. During mitochondrial-mediated apoptosis, multiple pathways converge on mitochondria and induce mitochondrial outer membrane permeabilization (MOMP). MOMP results in the release of intermembrane space proteins such as cytochrome c and Apaf1 into the cytosol where they activate the caspases and DNases that execute cell death. The precise molecular components of the pore(s) responsible for MOMP are unknown, but sphingolipids are thought to play a role. Here, we review evidence for a role of sphingolipids in the induction of mitochondrial-mediated apoptosis with a focus on potential underlying molecular mechanisms by which altered sphingolipid metabolism indirectly or directly induce MOMP. Data available on these mechanisms is reviewed, and the focus and limitations of previous and current studies are discussed to present important unanswered questions and potential future directions.

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“…The principal effect of inflammation on the intestine is the loss of function and structure of the intestinal mucosa and as a consequence failure in the absorption of nutrients, translocation of microbiota bacteria, and changes in the intestinal microenvironment that favor the development of pathogenic bacteria. Thus, S1P has a harmful role in inflammatory illnesses including IBD [ 48 ].…”

Section: Sphingosine-1-phosphate and Ibdmentioning

confidence: 99%

Sphingolipids as Mediators in the Crosstalk between Microbiota and Intestinal Cells: Implications for Inflammatory Bowel Disease

Phillips-Farfán

Karla

Alejandro

et al. 2016

Mediators of Inflammation

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Inflammatory bowel disease (IBD) describes different illnesses characterized by chronic inflammation of the gastrointestinal tract. Although the pathogenic mechanisms leading to IBD are poorly understood, immune system disturbances likely underlie its development. Sphingolipids (SLs) have been identified as important players and promising therapeutic targets to control inflammation in IBD. Interestingly, it seems that microorganisms of the normal gut microbiota and probiotics are involved in sphingolipid function. However, there is a great need to investigate the role of SLs as intermediates in the crosstalk between intestinal immunity and microorganisms. This review focuses on recent investigations that describe some mechanisms involved in the regulation of cytokine profiles by SLs. We also describe the importance of gut microbiota in providing signaling molecules that favor the communication between resident bacteria and intestinal cells. This, in turn, modulates the immune response in the bowel and likely in other peripheral organs. The potential of SLs and gut microbiota as targets or therapeutic agents for IBD is also discussed.

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Sphingosine kinase and sphingosine-1-phosphate: regulators in autoimmune and inflammatory disease

Cited by 29 publications

References 87 publications

The S1P–S1PR Axis in Neurological Disorders—Insights into Current and Future Therapeutic Perspectives

The S1P–S1PR Axis in Neurological Disorders—Insights into Current and Future Therapeutic Perspectives

Sphingolipids and mitochondrial apoptosis

Sphingolipids as Mediators in the Crosstalk between Microbiota and Intestinal Cells: Implications for Inflammatory Bowel Disease

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