Consequences of endogenous psychosine accumulation for Krabbe disease



Written on Wednesday 14 May 2014

Krabbe disease is a fatal neurodegenerative illness characterised by a progressive demyelination, against which there is no efficacious treatment.

This disease is caused by a deficiency of the galactocerebrosidase enzyme, leading to the toxic accumulation of psychosine primarily in myelin cells called oligodendrocytes. This increased amount of psychosine could cause the degeneration of oligodendrocytes and thus induce demyelination.
In the current study, the effects of the accumulation of endogenous psychosine induced experimentally on the fate and survival of oligodendrocytes is explored.
The excess of psychosine, by reducing the synthesis of myelin lipids and proteins and inducing the death of maturing oligodendrocytes, prevents the differentiation of oligodendrocytes.
The psychosine-induced pathological process implicates the activation of the secretory phospholipase A2 enzyme. Treatment with an inhibitor of this enzyme, the 7,7-dimethyleicosadienoic acid or DEDA, attenuates the process which leaves the hope of the possibility of a treatment for Krabbe disease.

Disease: Krabbe disease
Experimental model: Human myelin cells (oligodendrocytes)
Study type: Pathophysiology
Laboratory: Dr Ralph A. Johnson, Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, S.C., United States.

Source: J.S. Won, J. Kim, M.K. Paintlia, I. Singh, A.K. Singh. Role of endogenous psychosine accumulation in oligodendrocyte differentiation and survival: implication for Krabbe disease. Brain Res. 2013, 1508:44-52.

Scientific information provided in collaboration with the INIST-CNRS Institute, Institute for Scientific and Technical Information

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