Sphingolipids in neurodegeneration (with focus on ceramide and S1P)

Guanghu Wang, Erhard Bieberich

Research output: Contribution to journalReview articlepeer-review

53 Scopus citations


For many decades, research on sphingolipids associated with neurodegenerative disease focused on alterations in glycosphingolipids, particularly glycosylceramides (cerebrosides), sulfatides, and gangliosides. This seemed quite natural since many of these glycolipids are constituents of myelin and accumulated in lipid storage diseases (sphingolipidoses) resulting from enzyme deficiencies in glycolipid metabolism. With the advent of recognizing ceramide and its derivative, sphingosine-1-phosphate (S1P), as key players in lipid cell signaling and regulation of cell death and survival, research focus shifted toward these two sphingolipids. Ceramide and S1P are invoked in a plethora of cell biological processes participating in neurodegeneration such as ER stress, autophagy, dysregulation of protein and lipid transport, exosome secretion and neurotoxic protein spreading, neuroinflammation, and mitochondrial dysfunction. Hence, it is timely to discuss various functions of ceramide and S1P in neurodegenerative disease and to define sphingolipid metabolism and cell signaling pathways as potential targets for therapy.

Original languageEnglish
Pages (from-to)51-64
Number of pages14
JournalAdvances in Biological Regulation
StatePublished - Dec 2018

Bibliographical note

Funding Information:
This work was the supported by the National Institutes of Health grants NIH R01AG034389 and R01NS095215 . The authors also acknowledge support by the Department of Physiology (Chair Dr. Alan Daugherty), University of Kentucky , Lexington, KY.

Publisher Copyright:
© 2018 Elsevier Ltd

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Cancer Research


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