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Phosphatidylserine Increases IKBKAP Levels in Familial Dysautonomia Cells

Familial Dysautonomia (FD) is an autosomal recessive congenital neuropathy that results from abnormal development and progressive degeneration of the sensory and autonomic nervous system. The mutation observed in almost all FD patients is a point mutation at position 6 of intron 20 of the IKBKAP gen...

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Autores principales: Keren, Hadas, Donyo, Maya, Zeevi, David, Maayan, Channa, Pupko, Tal, Ast, Gil
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3012102/
https://www.ncbi.nlm.nih.gov/pubmed/21209961
http://dx.doi.org/10.1371/journal.pone.0015884
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author Keren, Hadas
Donyo, Maya
Zeevi, David
Maayan, Channa
Pupko, Tal
Ast, Gil
author_facet Keren, Hadas
Donyo, Maya
Zeevi, David
Maayan, Channa
Pupko, Tal
Ast, Gil
author_sort Keren, Hadas
collection PubMed
description Familial Dysautonomia (FD) is an autosomal recessive congenital neuropathy that results from abnormal development and progressive degeneration of the sensory and autonomic nervous system. The mutation observed in almost all FD patients is a point mutation at position 6 of intron 20 of the IKBKAP gene; this gene encodes the IκB kinase complex-associated protein (IKAP). The mutation results in a tissue-specific splicing defect: Exon 20 is skipped, leading to reduced IKAP protein expression. Here we show that phosphatidylserine (PS), an FDA-approved food supplement, increased IKAP mRNA levels in cells derived from FD patients. Long-term treatment with PS led to a significant increase in IKAP protein levels in these cells. A conjugate of PS and an omega-3 fatty acid also increased IKAP mRNA levels. Furthermore, PS treatment released FD cells from cell cycle arrest and up-regulated a significant number of genes involved in cell cycle regulation. Our results suggest that PS has potential for use as a therapeutic agent for FD. Understanding its mechanism of action may reveal the mechanism underlying the FD disease.
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spelling pubmed-30121022011-01-05 Phosphatidylserine Increases IKBKAP Levels in Familial Dysautonomia Cells Keren, Hadas Donyo, Maya Zeevi, David Maayan, Channa Pupko, Tal Ast, Gil PLoS One Research Article Familial Dysautonomia (FD) is an autosomal recessive congenital neuropathy that results from abnormal development and progressive degeneration of the sensory and autonomic nervous system. The mutation observed in almost all FD patients is a point mutation at position 6 of intron 20 of the IKBKAP gene; this gene encodes the IκB kinase complex-associated protein (IKAP). The mutation results in a tissue-specific splicing defect: Exon 20 is skipped, leading to reduced IKAP protein expression. Here we show that phosphatidylserine (PS), an FDA-approved food supplement, increased IKAP mRNA levels in cells derived from FD patients. Long-term treatment with PS led to a significant increase in IKAP protein levels in these cells. A conjugate of PS and an omega-3 fatty acid also increased IKAP mRNA levels. Furthermore, PS treatment released FD cells from cell cycle arrest and up-regulated a significant number of genes involved in cell cycle regulation. Our results suggest that PS has potential for use as a therapeutic agent for FD. Understanding its mechanism of action may reveal the mechanism underlying the FD disease. Public Library of Science 2010-12-29 /pmc/articles/PMC3012102/ /pubmed/21209961 http://dx.doi.org/10.1371/journal.pone.0015884 Text en Keren et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Keren, Hadas
Donyo, Maya
Zeevi, David
Maayan, Channa
Pupko, Tal
Ast, Gil
Phosphatidylserine Increases IKBKAP Levels in Familial Dysautonomia Cells
title Phosphatidylserine Increases IKBKAP Levels in Familial Dysautonomia Cells
title_full Phosphatidylserine Increases IKBKAP Levels in Familial Dysautonomia Cells
title_fullStr Phosphatidylserine Increases IKBKAP Levels in Familial Dysautonomia Cells
title_full_unstemmed Phosphatidylserine Increases IKBKAP Levels in Familial Dysautonomia Cells
title_short Phosphatidylserine Increases IKBKAP Levels in Familial Dysautonomia Cells
title_sort phosphatidylserine increases ikbkap levels in familial dysautonomia cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3012102/
https://www.ncbi.nlm.nih.gov/pubmed/21209961
http://dx.doi.org/10.1371/journal.pone.0015884
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