Ceramide and
sphingosine display a unique profile during brain development, indicating their critical role in myelinogenesis. Employing advanced technology such as gas chromatography-mass spectrometry, high performance liquid chromatography, and immunocytochemistry, along with cell culture and molecular biology, we have found an accumulation of
sphingosine in brain tissues of patients with
multiple sclerosis (MS) and in the spinal cord of rats induced with
experimental autoimmune encephalomyelitis. The elevated
sphingosine leads to oligodendrocyte death and fosters
demyelination.
Ceramide elevation by
serine palmitoyltransferse (SPT) activation was the primary source of the
sphingosine elevation as
myriocin, an inhibitor of SPT, prevented
sphingosine elevation and protected oligodendrocytes. Supporting this view,
fingolimod, a
drug used for MS
therapy, reduced
ceramide generation, thus offering partial protection to oligodendrocytes.
Sphingolipid synthesis and degradation in normal development is regulated by a series of
microRNAs (
miRNAs), and hence, accumulation of
sphingosine in MS may be prevented by employing
miRNA technology. This review will discuss the current knowledge of
ceramide and
sphingosine metabolism (synthesis and breakdown), and how their biosynthesis can be regulated by
miRNA, which can be used as a therapeutic approach for MS.