PUBLICATION
Endothelial cell dysfunction in globoid cell leukodystrophy
- Authors
- Belleri, M., Presta, M.
- ID
- ZDB-PUB-160403-7
- Date
- 2016
- Source
- Journal of neuroscience research 94(11): 1359-67 (Review)
- Registered Authors
- Presta, Marco
- Keywords
- Krabbe disease, angiogenesis, central nervous system, endothelial cells, psychosine, twitcher mouse
- MeSH Terms
-
- Animals
- Brain/pathology*
- Computer Simulation
- Endothelial Cells/pathology*
- Endothelial Cells/ultrastructure
- Galactosylceramidase/deficiency
- Galactosylceramidase/genetics
- Humans
- Leukodystrophy, Globoid Cell/pathology*
- Microvessels/pathology*
- Microvessels/ultrastructure
- Psychosine/metabolism
- PubMed
- 27037626 Full text @ J. Neurosci. Res.
Citation
Belleri, M., Presta, M. (2016) Endothelial cell dysfunction in globoid cell leukodystrophy. Journal of neuroscience research. 94(11):1359-67.
Abstract
Angiogenesis plays a pivotal role in the physiology and pathology of the brain. Microvascular alterations have been observed in various neurodegenerative disorders, including genetic leukodystrophies. Globoid cell leukodystrophy (GLD) is a lysosomal storage disease caused by β-galactosylceramidase (GALC) deficiency and characterized by the accumulation of the neurotoxic metabolite psychosine in the central nervous system and peripheral tissues. Structural and functional alterations occur in the microvascular endothelium of the brain of GLD patients and twitcher mice, a murine model of the disease. In addition, increased vessel permeability and a reduced capacity to respond to proangiogenic stimuli characterize the endothelium of twitcher animals. On the one hand, these alterations may depend, at least in part, on the local and systemic angiostatic activity exerted by psychosine on endothelial cells. On the other hand, studies performed in vivo on zebrafish embryos and in vitro on human endothelial cells suggest that GALC downregulation may also lead to psychosine-independent neuronal and vascular defects. Together, experimental observations indicate that endothelial cell dysfunctions may represent a novel pathogenic mechanism in human leukodystrophies, including GLD. A better understanding of the molecular mechanisms responsible for these microvascular alterations may provide new insights for the therapy of GLD.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping