Sphingosine kinase 2 in autoimmune/inflammatory disease and the development of sphingosine kinase 2 inhibitors
Open accessAbstract
The purpose of this Opinion is to present a case for targeting sphingosine kinase 2 (SK2) in autoimmune/inflammatory disease. Data obtained using Sphk2-/- mice suggest that SK2 is an anti-inflammatory enzyme, although this might be misleading because of a compensatory increase in the expression of a second isoform, sphingosine kinase 1 (SK1), which functions as a proinflammatory enzyme. SK2 is involved in regulating interleukin (IL)-12/interferon gamma (IFN-γ) and histone deacetylase-1/2 (HDAC-1/2) signalling and, potentially, retinoid-related orphan receptor gamma t (ROR-γt) stability linked with T helper (Th) 17 cell polarisation. Therefore, there is a need to develop highly potent SK2 inhibitors with selectivity over SK1 to clearly define the role of SK2 in autoimmune/inflammatory disease. Structural determinants of SK2 relative to SK1 will enable the design of selective SK2 inhibitors.
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SphK2 inhibitor has anti-inflammatory activity in several diseases.
“and SphK2 inhibitor has anti-inflammatory activity in several diseases (40).”
From Nuclear SphK2/S1P signaling is a key regulator of ApoE production and Aβ uptake in astrocytes (2024) · cites this paper as [40]
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Nuclear SphK2/S1P signaling is a key regulator of ApoE production and Aβ uptake in astrocytes
Komai, M., Noda, Y., Ikeda, A., Kaneshiro, N., Kamikubo, Y., Sakurai, T., Uehara, T., & Takasugi, N. (2024) · Journal of Lipid Research · doi:10.1016/j.jlr.2024.100510 · Cited by 13 · see citing works
- Authors
- Pyne, N. J., Adams, D. R., & Pyne, S.
- Affiliations
- University of Strathclyde (GB)
- Heriot-Watt University (GB)
- Corresponding author
- Pyne, Nigel J.
- Venue
- Trends in Pharmacological Sciences
- Publisher
- Elsevier BV
- Published
- 2017-07
- Volume
- 38
- Issue
- 7
- Pages
- 581-591
- ISSN
- 0165-6147 (ISSN-L)
- OpenAlex
- W2624184959
- Cited by
- 43
- References
- 1
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 6 · 2023: 4 · 2022: 6 · 2021: 5 · 2020: 7 · 2019: 5 · 2018: 5 · 2017: 1
- FWCI
- 0.47
- Type
- journal article
- Language
- en
- Open access
- Locations
- Trends in Pharmacological Sciences (publishedVersion)
- PubMed (publishedVersion)
- Strathprints: The University of Strathclyde institutional repository (University of Strathclyde) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- sphingosine kinase 2, sphingosine kinase 1, autoimmune disease, inflammatory diseases, RORγt, anti-inflammatory enzymes
- MeSH terms
- Sphingosine Kinase, Animals, Autoimmune Diseases, Humans, Inflammation, Phosphotransferases (Alcohol Group Acceptor), Protein Kinase Inhibitors
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