NeuroMolecular Medicine

, Volume 18, Issue 3, pp 396–414 | Cite as

Biological Effects of Naturally Occurring Sphingolipids, Uncommon Variants, and Their Analogs

  • Mitchell K. P. Lai
  • Wee Siong Chew
  • Federico Torta
  • Angad Rao
  • Greg L. Harris
  • Jerold Chun
  • Deron R. HerrEmail author
Review Paper


Sphingolipids (SPs) comprise a highly diverse class of lipids that serve biological roles both as structural components of cell membranes and as mediators of cell signaling. Pharmacologic and genetic manipulation of SPs and their signaling systems have underscored their importance in most biological processes, including central nervous system development and function. Likewise, perturbations of SP accumulation or signaling have been associated with a number of disease states, such as neural tube defects, neuroinflammation, stroke, and dementia. SPs can be endogenously synthesized de novo, and their metabolism is a well-regulated process, so their value as nutraceuticals has not been scrutinized. However, there is evidence that sphingolipid-rich diets can affect lipid homeostasis, and several mycotoxins are SP analogs that are known to cause profound derangement of SP metabolism or signaling. Furthermore, plants and invertebrates have SP species that are not present in mammals. Several of these have been shown to induce biological responses in mammalian cells. These findings suggest that dietary intake of SPs or SP analogs may have significant effects on human health or disease outcome. This manuscript provides an overview of SP metabolism and signaling, their perturbations in neurological diseases, as well as potential impacts of modulating this system in the brain.


Sphingolipid Fingolimod Nutraceutical Sphingosine 1-phosphate receptor Ceramide Review 


Compliance with Ethical Standards

Conflict of interest

D.R.H. and G.L.H. have received consulting fees or grant support from Expression Drug Designs, LLC and Bayer Healthcare. J.C. has received honoraria, consulting fees and/or grant support from: Abbott, Amira Pharmaceuticals, Biogen-Idec, Celgene, GlaxoSmithKline, Johnson and Johnson, Merck, Mitsubishi Tanabe Pharma Corporation, Novartis, Ono Pharmaceutical Co., Pfizer and Taisho Pharmaceutical Co. M.K.P.L., W.S.C., F.T., and A.R. have no financial relationships to declare.


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© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Department of Pharmacology, Yong Loo Lin School of MedicineNational University of SingaporeKent RidgeSingapore
  2. 2.Department of Biochemistry, Yong Loo Lin School of MedicineNational University of SingaporeKent RidgeSingapore
  3. 3.Department of BiologySan Diego State UniversitySan DiegoUSA
  4. 4.Department of Molecular and Cellular Neuroscience, Dorris Neuroscience CenterThe Scripps Research InstituteLa JollaUSA

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