ArticleJournal of inherited metabolic disease2000
The increased sensitivity of neurons with elevated glucocerebroside to neurotoxic agents can be reversed by imiglucerase.
Article in Journal of inherited metabolic disease, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 45 citations in OpenAlex.
- Exploring genetic modifiers of Gaucher disease: The next horizon.Human mutation · 2018Review
- A new glucocerebrosidase-deficient neuronal cell model provides a tool to probe pathophysiology and therapeutics for Gaucher disease.Disease models & mechanisms · 2016Article
- Long-term follow-up and sudden unexpected death in Gaucher disease type 3 in Egypt.Neurology. Genetics · 2016Article
- Evoked potentials and neurocognitive functions in pediatric Egyptian Gaucher patients on enzyme replacement therapy: a single center experience.Journal of inherited metabolic disease · 2013Article
- Article
- New therapeutic options for lysosomal storage disorders: enzyme replacement, small molecules and gene therapy.Human genetics · 2007Review
- Diabetes alters sphingolipid metabolism in the retina: a potential mechanism of cell death in diabetic retinopathy.Diabetes · 2006Article
- Upregulation of proinflammatory cytokines in the fetal brain of the Gaucher mouse.Journal of Korean medical science · 2006Article
- Down-regulation of Bcl-2 in the fetal brain of the Gaucher disease mouse model: a possible role in the neuronal loss.Journal of human genetics · 2004Article
- Glycosphingolipidoses: beyond the enzymatic defect.Glycoconjugate journal · 2004Review
- Lyso-glycosphingolipids mobilize calcium from brain microsomes via multiple mechanisms.The Biochemical journal · 2003Article
- A model of neuronopathic Gaucher disease.Journal of inherited metabolic disease · 2003Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We have recently demonstrated that incubation of cultured rat hippocampal neurons with conduritol beta-epoxide (CBE), an inhibitor of glucocerebrosidase, the enzyme defective in Gaucher disease, results in changes in intracellular morphology and in functional calcium stores. Changes in levels of functional calcium stores are directly related to neuronal cell death. We now show that neurons incubated with either CBE or a non-hydrolysable analogue of GlcCer (glucosylthioceramide), are more sensitive to the toxic effects of high concentrations of glutamate and of a variety of metabolic inhibitors. A linear relationship exists between level of accumulation of GlcCer and the extent of neuronal cell death. The deleterious effects of elevated GlcCer levels can be completely reversed by addition of human glucocerebrosidase (imiglucerase) to the culture medium. Imiglucerase is internalized to lysosomes, where it presumably degrades excess GlcCer. This suggests that the limited success of enzyme replacement therapy in neuronopathic forms of Gaucher disease is not due to lack of efficacy of glucocerebroside in degrading GlcCer in neurons of the central nervous system, and adds impetus to attempts to develop ways to efficiently deliver glucocerebrosidase to the brains of neurologically compromised Gaucher disease patients.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.