Impairment of ceramide synthesis causes a novel progressive myoclonus epilepsy
Abstract
Objective: Alterations of sphingolipid metabolism are implicated in the pathogenesis of many neurodegenerative disorders. Methods: We identified a homozygous nonsynonymous mutation in CERS1, the gene encoding ceramide synthase 1, in 4 siblings affected by a progressive disorder with myoclonic epilepsy and dementia. CerS1, a transmembrane protein of the endoplasmic reticulum (ER), catalyzes the biosynthesis of C18‐ceramides. Results: We demonstrated that the mutation decreases C18‐ceramide levels. In addition, we showed that downregulation of CerS1 in a neuroblastoma cell line triggers ER stress response and induces proapoptotic pathways. Interpretation: This study demonstrates that impairment of ceramide biosynthesis underlies neurodegeneration in humans. Ann Neurol 2014;76:206–212
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Structure information is not available for any of the CerS enzymes or their homologs, and the number and orientation of transmembrane helices are not known.
“Structure information is not available for any of the CerS enzymes or their homologs, and the number and orientation of transmembrane helices (TMH) are not known (28).”
From Accurate prediction of protein structures and interactions using a 3-track network (2021) · cites this paper as [28]
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- Authors
- Vanni, N., Fruscione, F., Ferlazzo, E., Striano, P., Robbiano, A., Traverso, M., Sander, T., Falace, A., Gazzerro, E., Bramanti, P., Bielawski, J., Fassio, A., Minetti, C., Genton, P., & Zara, F.
- Affiliations
- Istituto Giannina Gaslini (IT)
- Magna Graecia University (IT)
- University of Cologne (DE)
- University of Genoa (IT)
- Centro Neurolesi Bonino Pulejo (IT)
- Medical University of South Carolina (US)
- Henri Gastaut Hospital (FR)
- Corresponding author
- Zara, Federico
- ORCID
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2014-05-20
- Volume
- 76
- Issue
- 2
- Pages
- 206-212
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- OpenAlex
- W2154467573
- Cited by
- 94
- References
- 23
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 5 · 2023: 6 · 2022: 10 · 2021: 13 · 2020: 9 · 2019: 7 · 2018: 7 · 2017: 7 · 2016: 10 · 2015: 4 · 2014: 2
- FWCI
- 3.14
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
- CINECA IRIS Institutial Research Information System (University of Genoa) (submittedVersion)
- Funders
- Italian Ministry of Health (RF-2010-2314356)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Keywords
- progressive myoclonic epilepsy, CERS1, ceramide biosynthesis, sphingolipid metabolism, homozygous mutation, endoplasmic reticulum stress, apoptosis, neurodegeneration
- MeSH terms
- Algeria, Ceramides, Dementia, Endoplasmic Reticulum, Humans, Membrane Proteins, Mutation, Myoclonic Epilepsies, Progressive, Siblings, Sphingosine N-Acyltransferase
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