Tocotrienols induce IKBKAP expression: a possible therapy for familial dysautonomia

Biochem Biophys Res Commun. 2003 Jun 20;306(1):303-9. doi: 10.1016/s0006-291x(03)00971-9.


Familial dysautonomia (FD), a neurodegenerative genetic disorder primarily affecting individuals of Ashkenazi Jewish descent, is caused by mutations in the IKBKAP gene which encodes the IkappaB kinase complex-associated protein (IKAP). The more common or major mutation causes aberrant splicing, resulting in a truncated form of IKAP. Tissues from individuals homozygous for the major mutation contain both mutant and wild-type IKAP transcripts. The apparent leaky nature of this mutation prompted a search for agents capable of elevating the level of expression of the wild-type IKAP transcript. We report the ability of tocotrienols, members of the vitamin E family, to increase transcription of IKAP mRNA in FD-derived cells, with corresponding increases in the correctly spliced transcript and normal protein. These findings suggest that in vivo supplementation with tocotrienols may elevate IKBKAP gene expression and in turn increase the amount of functional IKAP protein produced in FD patients.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism*
  • Cell Line
  • DNA Primers / genetics
  • Dysautonomia, Familial / drug therapy*
  • Dysautonomia, Familial / genetics*
  • Dysautonomia, Familial / metabolism
  • Exons
  • Gene Expression / drug effects
  • Humans
  • Kinetics
  • Mutation*
  • RNA Splicing / drug effects
  • RNA Splicing / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Tissue Distribution
  • Tocotrienols / pharmacology*
  • Tocotrienols / therapeutic use
  • Transcription, Genetic / drug effects
  • Transcriptional Elongation Factors
  • Vitamin E / analogs & derivatives*
  • Vitamin E / pharmacology
  • Vitamin E / therapeutic use


  • Carrier Proteins
  • DNA Primers
  • Elp1 protein, human
  • RNA, Messenger
  • Tocotrienols
  • Transcriptional Elongation Factors
  • Vitamin E
  • tocotrienol, delta