title: Biological Effects of Naturally Occurring Sphingolipids, Uncommon Variants, and Their Analogs.
abstract: 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.
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge, Singapore.
authors.forename: Mitchell K P
authors.initials: MK
authors.lastname: Lai
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge, Singapore.
authors.forename: Wee Siong
authors.initials: WS
authors.lastname: Chew
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge, Singapore.
authors.forename: Federico
authors.initials: F
authors.lastname: Torta
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge, Singapore.
authors.forename: Angad
authors.initials: A
authors.lastname: Rao
authors.affiliation: Department of Biology, San Diego State University, San Diego, CA, USA.
authors.forename: Greg L
authors.initials: GL
authors.lastname: Harris
authors.affiliation: Department of Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Jerold
authors.initials: J
authors.lastname: Chun
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge, Singapore. phcdrh@nus.edu.sg.|Department of Biology, San Diego State University, San Diego, CA, USA. phcdrh@nus.edu.sg.
authors.forename: Deron R
authors.identifier: http://orcid.org/0000-0001-5755-0896
authors.initials: DR
authors.lastname: Herr
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects; D006706:Homeostasis; D006801:Humans; D015398:Signal Transduction / Q000187:drug effects; D013107:Sphingolipids / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D013107:Sphingolipids
keywords: Ceramide; Fingolimod; Nutraceutical; Review; Sphingolipid; Sphingosine 1-phosphate receptor