{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T02:17:43Z","timestamp":1791685063484,"version":"4.3.4"},"reference-count":141,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,8,30]],"date-time":"2022-08-30T00:00:00Z","timestamp":1661817600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ABN and Guarantors of Brain and an Irish Institute of Clinical Neuroscience"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/jpm12091418","type":"journal-article","created":{"date-parts":[[2022,8,31]],"date-time":"2022-08-31T00:13:56Z","timestamp":1661904836000},"page":"1418","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["The Role of Sphingomyelin and Ceramide in Motor Neuron Diseases"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1008-598X","authenticated-orcid":false,"given":"Gavin","family":"McCluskey","sequence":"first","affiliation":[{"name":"Personalised Medicine Center, School of Medicine, Ulster University, Derry BT47 6SB, UK"},{"name":"Department of Neurology, Altnagelvin Hospital, Derry, BT47 6SB, UK"},{"name":"Department of Neurology, Royal Victoria Hospital, Belfast BT12 6BA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colette","family":"Donaghy","sequence":"additional","affiliation":[{"name":"Department of Neurology, Altnagelvin Hospital, Derry, BT47 6SB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen E.","family":"Morrison","sequence":"additional","affiliation":[{"name":"Department of Neurology, Royal Victoria Hospital, Belfast BT12 6BA, UK"},{"name":"Faculty of Medicine, Health & Life Sciences, Queen\u2019s University, Belfast BT9 6AG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"McConville","sequence":"additional","affiliation":[{"name":"Department of Neurology, Royal Victoria Hospital, Belfast BT12 6BA, UK"},{"name":"Department of Neurology, Ulster Hospital, Dundonald, Belfast BT16 1RH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2239-9094","authenticated-orcid":false,"given":"William","family":"Duddy","sequence":"additional","affiliation":[{"name":"Personalised Medicine Center, School of Medicine, Ulster University, Derry BT47 6SB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6510-5426","authenticated-orcid":false,"given":"Stephanie","family":"Duguez","sequence":"additional","affiliation":[{"name":"Personalised Medicine Center, School of Medicine, Ulster University, Derry BT47 6SB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"723871","DOI":"10.3389\/fnagi.2021.723871","article-title":"Motor Neuron Diseases and Neuroprotective Peptides: A Closer Look to Neurons","volume":"13","author":"Zuccaro","year":"2021","journal-title":"Front. 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