Globoid cell leukodystrophy (Krabbe disease) is characterized by the 
accumulation of a toxic metabolite, psychosine (galactosylsphingosine), which is 
a substrate for the deficient enzyme (galactocerebroside beta-galactosidase). 
This study underscores the possible role of psychosine in the effect of 
inducible nitric oxide synthase (iNOS) -derived NO in the pathophysiology of 
this demyelinating disease. For the first time, we provide evidence of the 
expression of iNOS in CNS of Krabbe patient and show that the iNOS-expressing 
cells in the CNS were astrocytes. Psychosine potentiated the LPS-induced 
production of proinflammatory cytokines (IL-1beta, IL-6, and TNF-alpha) in 
primary rat astrocytes and regulated the cytokine-mediated production of NO in 
C6 glioma and primary rat astrocyte. Psychosine induced cytokine-mediated 
nuclear translocation of AP-1 and C/EBP by potentiating the expression of Fra-1 
and C/EBP-delta proteins. This suggests that psychosine maintained or sustained 
the cytokine-primed expression of iNOS by further potentiating the nuclear 
translocation of AP-1 and C/EBP without modulating the cytokine-mediated 
transcription activity of NF-kappaB. This study hypothesizes that accumulated 
psychosine leads to production of cytokines and iNOS expression. The ensuing 
excessive production of NO and ONOO- may play a role in pathogenesis of Krabbe 
disease.