Ceramide synthases as potential targets for therapeutic intervention in human diseases

Joo Won Park, Woo Jae Park, Anthony H. Futerman

Research output: Contribution to journalReview articlepeer-review

182 Scopus citations

Abstract

Ceramide is located at a key hub in the sphingolipid metabolic pathway and also acts as an important cellular signaling molecule. Ceramide contains one acyl chain which is attached to a sphingoid long chain base via an amide bond, with the acyl chain varying in length and degree of saturation. The identification of a family of six mammalian ceramide synthases (CerS) that synthesize ceramide with distinct acyl chains, has led to significant advances in our understanding of ceramide biology, including further delineation of the role of ceramide in various pathophysiologies in both mice and humans. Since ceramides, and the complex sphingolipids generated from ceramide, are implicated in disease, the CerS might potentially be novel targets for therapeutic intervention in the diseases in which the ceramide acyl chain length is altered. This article is part of a Special Issue entitled New Frontiers in Sphingolipid Biology.

Original languageEnglish
Pages (from-to)671-681
Number of pages11
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1841
Issue number5
DOIs
StatePublished - May 2014

Bibliographical note

Funding Information:
We thank Rotem Tidhar for help in making Fig. 1 and Dr. Shifra Ben-Dor (Bioinformatics and Biological Computing Unit, Weizmann Institute of Science) for critical comments. Work in the Futerman Laboratory on the CerS is supported by the Minerva Foundation , the Israel Science Foundation ( 0888/11 ) and the National Institutes of Health ( GM076217 ). W-J. Park was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology ( 2012R1A6A3A03038319 ). Anthony H. Futerman is the Joseph Meyerhoff Professor of Biochemistry at the Weizmann Institute of Science.

Keywords

  • Acyl chain length
  • Ceramide synthase
  • Disease
  • Specificity
  • Sphingolipid
  • Therapeutic target

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