| First Author | Smith NJ | Year | 2018 |
| Journal | J Pathol | Volume | 244 |
| Issue | 1 | Pages | 120-128 |
| PubMed ID | 28981147 | Mgi Jnum | J:253746 |
| Mgi Id | MGI:6102466 | Doi | 10.1002/path.4992 |
| Citation | Smith NJ, et al. (2018) Reduced cerebral vascularization in experimental neuronopathic Gaucher disease. J Pathol 244(1):120-128 |
| abstractText | The glycosphingolipidosis, Gaucher disease, in which a range of neurological manifestations occur, results from a deficiency of acid beta-glucocerebrosidase, with subsequent accumulation of beta-glucocerebroside, its upstream substrates, and the non-acylated congener beta-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 beta-glucosylsphingosine. Further in vitro studies confirmed a concentration-dependent impairment of endothelial cytokinesis upon exposure to quasi-pathological concentrations of beta-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. Copyright (c) 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. |
