title: Phosphatidylserine increases IKBKAP levels in familial dysautonomia cells.
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 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.
authors.affiliation: Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel. gilast@post.tau.ac.il
authors.forename: Hadas
authors.initials: H
authors.lastname: Keren
authors.forename: Maya
authors.initials: M
authors.lastname: Donyo
authors.forename: David
authors.initials: D
authors.lastname: Zeevi
authors.forename: Channa
authors.initials: C
authors.lastname: Maayan
authors.forename: Tal
authors.initials: T
authors.lastname: Pupko
authors.forename: Gil
authors.initials: G
authors.lastname: Ast
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism*; D002453:Cell Cycle; D002460:Cell Line; D016000:Cluster Analysis; D003062:Codon; D004402:Dysautonomia, Familial / Q000235:genetics* / Q000378:metabolism*; D015525:Fatty Acids, Omega-3 / Q000378:metabolism; D005786:Gene Expression Regulation; D006579:Heterozygote; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D007438:Introns; D020411:Oligonucleotide Array Sequence Analysis; D010718:Phosphatidylserines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D035602:Transcriptional Elongation Factors
chemical_list: D002352:Carrier Proteins; D003062:Codon; C114720:Elp1 protein, human; D015525:Fatty Acids, Omega-3; D010718:Phosphatidylserines; D012333:RNA, Messenger; D035602:Transcriptional Elongation Factors; D051550:I-kappa B Kinase