Annals of neurology · 2014
Impairment of ceramide synthesis causes a novel progressive myoclonus epilepsy.
Клинический случайСтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Vanni Nicola, Fruscione Floriana, Ferlazzo Edoardo, Striano Pasquale, Robbiano Angela, Traverso Monica, Sander Thomas, Falace Antonio, Gazzerro Elisabetta, Bramanti Placido, Bielawski Jacek, Fassio Anna, Minetti Carlo, Genton Pierre, Zara Federico
Аннотация
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.
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.