Ontology highlight
ABSTRACT:
SUBMITTER: Hait NC
PROVIDER: S-EPMC4256678 | biostudies-literature | 2014 Jul
REPOSITORIES: biostudies-literature
Hait Nitai C NC Wise Laura E LE Allegood Jeremy C JC O'Brien Megan M Avni Dorit D Reeves Thomas M TM Knapp Pamela E PE Lu Junyan J Luo Cheng C Miles Michael F MF Milstien Sheldon S Lichtman Aron H AH Spiegel Sarah S
Nature neuroscience 20140525 7
FTY720 (fingolimod), an FDA-approved drug for treatment of multiple sclerosis, has beneficial effects in the CNS that are not yet well understood, independent of its effects on immune cell trafficking. We show that FTY720 enters the nucleus, where it is phosphorylated by sphingosine kinase 2 (SphK2), and that nuclear FTY720-P binds and inhibits class I histone deacetylases (HDACs), enhancing specific histone acetylations. FTY720 is also phosphorylated in mice and accumulates in the brain, includ ...[more]