Disruption of neovascularization in Krabbe disease

Written on Tuesday 23 September 2014

Krabbe disease, also known as globoid cell leukodystrophy, is a neurologic illness caused by the lack of a protein called β-galactosylceramidase, which leads to the abnormal accumulation of a toxic component, psychosine, in the central nervous system (brain and spinal cord).

This disease is characterized by an alteration in the cells that synthesize myelin, known as oligodendrocytes, and a progressive destruction of the myelin in the central and peripheral nervous systems, resulting in death before the age of two years.

Neovascularization, i.e. the growth of new blood vessels from pre-existing vessels, plays an important role in brain development. This study allowed deleterious effects of low doses of psychosine on neovascularization to be observed. Thus, major alterations of the cells coating the small blood vessels were seen in the brains of sick new-born mice. These cells also show a reduced ability to respond to the factors needed for neovascularization. However, this ability is restored when the expression of the gene coding for β-galactosylceramidase is allowed.

The cellular alterations observed in the micro-vessels were also found in a brain biopsy taken from a patient.

The lack of β-galactosylceramidase thus induces major disruptions in the neovascularization of the central nervous system, which could contribute to the development of brain lesions in patients suffering from Krabbe disease.

Disease: Krabbe disease
Experimental model: Twitcher mice, the model for Krabbe disease
Study type: Pathophysiology
Laboratory: Dr Marco Presta, Department of Molecular and Translational Medecine, School of  Medecine, University of Brescia, Italy

Source : M. Belleri, R. Ronca, D. Coltrini, B. Nico, D. Ribatti, P.L. Poliani, A. Giacomini, P. Alessi, S. Marchesini, M.B. Santos, E.R. Bongarzone, M. Presta. Inhibition of angiogenesis by β-galactosylceramidase deficiency in globoid cell leukodystrophy. Brain 2013, 136(Pt 9):2859-75.

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