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Summary: Phosphatidylserine Increases IKBKAP Levels in Familial
Dysautonomia Cells
Hadas Keren1
*, Maya Donyo1
, David Zeevi2
, Channa Maayan3
, Tal Pupko2
, Gil Ast1
1 Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel, 2 Department of Cell Research and
Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv, Israel, 3 Department of Pediatrics, Hadassah University Hospital, Mount Scopus,
Jerusalem, Israel
Abstract
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 IkB 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
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