Reduced cerebral vascularization in experimental neuronopathic Gaucher disease.
The Journal of pathology
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Smith, N. J., Fuller, M., Saville, J. T., & Cox, T. (2018). Reduced cerebral vascularization in experimental neuronopathic Gaucher disease.. The Journal of pathology, 244 (1), 120-128. https://doi.org/10.1002/path.4992
ABSTRACT The glycosphingolipidosis Gaucher disease, in which a range of neurological manifestations occur, results from a deficiency of acid β-glucocerebrosidase, with subsequent accumulation of β-glucocerebroside, its upstream substrates and the unacylated congener, ß-glucosylsphingosine. However, the mechanisms by which end-organ dysfunction arise are poorly understood. Here we report strikingly diminished cerebral microvascular density in a murine model of disease and provide a detailed analysis of the accompanying cerebral glycosphingolipidome in these animals, with marked elevations of ß-glucosylsphingosine. Further in vitro studies confirm a concentration dependent impairment of endothelial cytokinesis upon exposure to quasi-pathological concentrations of ß-glucosylsphingosine. These findings support a premise for pathogenic disruption of cerebral angiogenesis as an end-organ effect, with potential for therapeutic modulation in neuronopathic Gaucher disease.
Brain, Animals, Humans, Mice, Gaucher Disease, Disease Models, Animal, Neovascularization, Pathologic, Psychosine, Microvessels
External DOI: https://doi.org/10.1002/path.4992
This record's URL: https://www.repository.cam.ac.uk/handle/1810/270706