The role of sphingomyelin and ceramide in motor neuron diseases

Gavin McCluskey, Colette Donaghy, Karen E. Morrison, John McConville, William Duddy, Stephanie Duguez*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

6 Citations (Scopus)
56 Downloads (Pure)

Abstract

Amyotrophic Lateral Sclerosis (ALS), Spinal Bulbar Muscular Atrophy (SBMA), and Spinal Muscular Atrophy (SMA) are motor neuron diseases (MNDs) characterised by progressive motor neuron degeneration, weakness and muscular atrophy. Lipid dysregulation is well recognised in each of these conditions and occurs prior to neurodegeneration. Several lipid markers have been shown to predict prognosis in ALS. Sphingolipids are complex lipids enriched in the central nervous system and are integral to key cellular functions including membrane stability and signalling pathways, as well as being mediators of neuroinflammation and neurodegeneration. This review highlights the metabolism of sphingomyelin (SM), the most abundant sphingolipid, and of its metabolite ceramide, and its role in the pathophysiology of neurodegeneration, focusing on MNDs. We also review published lipidomic studies in MNDs. In the 13 studies of patients with ALS, 12 demonstrated upregulation of multiple SM species and 6 demonstrated upregulation of ceramides. SM species also correlated with markers of clinical progression in five of six studies. These data highlight the potential use of SM and ceramide as biomarkers in ALS. Finally, we review potential therapeutic strategies for targeting sphingolipid metabolism in neurodegeneration.

Original languageEnglish
Article number1418
JournalJournal of Personalized Medicine
Volume12
Issue number9
Early online date30 Aug 2022
DOIs
Publication statusPublished - Sept 2022

Bibliographical note

Funding Information:
G.McC was a recipient of the Association of British Neurologists (ABN) Clinical Research Fellowship funded by the ABN and Guarantors of Brain and an Irish Institute of Clinical Neuroscience research grant.

Publisher Copyright:
© 2022 by the authors.

Keywords

  • Amyotrophic Lateral Sclerosis
  • ceramide
  • motor neuron disease
  • sphingolipid
  • sphingomyelin

ASJC Scopus subject areas

  • Medicine (miscellaneous)

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