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Ann Neurol. 2014 Aug;76(2):206-12. doi: 10.1002/ana.24170. Epub 2014 May 20.

Impairment of ceramide synthesis causes a novel progressive myoclonus epilepsy.

Author information

1
Department of Neuroscience, Institute G. Gaslini, Genoa, Italy.

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.

PMID:
24782409
DOI:
10.1002/ana.24170
[Indexed for MEDLINE]

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