The role of S1P receptors and their interacting proteins in Krabbe Disease
Citation:
Catherine O'Sullivan, 'The role of S1P receptors and their interacting proteins in Krabbe Disease', [thesis], Trinity College (Dublin, Ireland). Department of Physiology, 2015, pp 184Download Item:
Abstract:
Globoid cell leukodystrophy (Krabbe disease, KD) is a rare autosomal recessive
neurodegenerative disorder that presents within the first six months of life and is
usually fatal by the age of two years. KD is caused by a deficiency in the lysosomal
enzyme galactocerebrosidase (GALC), which results in the accumulation of the toxic
metabolite psychosine in the brain. Here we investigated the ability of psychosine to
directly induce hallmarks of KD, in vitro, focusing on increased levels of glial cell death,
mitochondrial dysfunction, pro-inflammatory cytokines and demyelination.
Importantly we also demonstrate reversal of these effects by the sphingosine 1-
phosphate receptor (SIPR) agonist pFTY720 (Fingolimod) (Results 1). We additionally
investigated effects of an S1PR1/S1PR5 agonist called BAF312 on psychosine-induced
toxicity in isolated astrocyte and microglia cultures as well as in slice culture models of
demyelination.
Author: O'Sullivan, Catherine
Advisor:
Dev, KumleshPublisher:
Trinity College (Dublin, Ireland). Department of PhysiologyNote:
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