Inhibiting glucosylceramide synthaseSynthase InhibitorsInhibition of glucosylceramide synthaseInhibitor of glucosylceramideHyaluronic acidPlasma ceramideSpleenGlycolipidGaucherGlucocerebrosidaseEnzymeCeramidesPhosphatidylethanolamineLysosomalGangliosidesAccumulationStructuralReductionProductionTherapyInhibitorGlycosphingolipidsSubstrateGlcCerAccumulatesGlucosylsphingosineSynthesisGolgiPrecursorFungalMembraneMetabolismIncreasesDevelopmentShown
Inhibiting glucosylceramide synthase2
- Reduces GSL production by inhibiting glucosylceramide synthase. (medscape.com)
- In contrast, substrate reduction therapy works by inhibiting glucosylceramide synthase, slowing the production of glucosylceramide. (medscape.com)
Synthase Inhibitors4
- The glucosylceramide synthase inhibitors, miglustat and eliglustat, were approved for adults with type 1 Gaucher disease in 2003 and 2014 respectively. (medscape.com)
- We treated both multidrug-resistant cell lines with the glucosylceramide synthase inhibitors PDMP (d-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol), C9DGJ (N-nonyl-deoxygalactonojirimycin) or C4DGJ (N-butyl-deoxygalactonojirimycin). (ox.ac.uk)
- However, the N-alkylated iminosugars C9DGJ and C4DGJ, which are more selective glucosylceramide synthase inhibitors than PDMP, failed to cause any reversal of drug resistance despite depleting glycolipids to the same extent as PDMP. (ox.ac.uk)
- 2023 ) Pyrazole Ureas as Low Dose, CNS Penetrant Glucosylceramide Synthase Inhibitors for the Treatment of Parkinson's Disease. (neurotree.org)
Inhibition of glucosylceramide synthase3
- Inhibition of glucosylceramide synthase does not reverse drug resistance in cancer cells. (ox.ac.uk)
- Our results suggest that (a) inhibition of glucosylceramide synthase does not reverse multidrug resistance and (b) the chemosensitization achieved by PDMP cannot be caused by inhibition of glucosylceramide synthase alone. (ox.ac.uk)
- Increased hepatic insulin action in diet-induced obese mice following inhibition of glucosylceramide synthase. (umassmed.edu)
Inhibitor of glucosylceramide1
- Eliglustat is a specific inhibitor of glucosylceramide synthase, thereby reducing production of glucosylceramide. (medscape.com)
Hyaluronic acid1
- As a product for those who want a healthy beauty, supplemented with outstanding beauty ingredients such as glucosylceramide 3,000mcg, hyaluronic acid, collagen. (asian-authentic.com)
Plasma ceramide2
- We reported that higher plasma ceramide and glucosylceramide levels were cross-sectionally associated with cognitive impairment in PD non-GBA mutations carriers. (mdsabstracts.org)
- Our results suggest that a higher plasma ceramide to glucosylceramide C18:0 ratio is predictive of greater rates of cognitive decline in cognitively normal PD patients and may be a potential blood-based prognostic cognitive biomarker. (mdsabstracts.org)
Spleen3
- The disease occurs when the lipid glucosylceramide accumulates in the bone marrow, lungs, spleen, liver, and sometimes the brain. (medscape.com)
- Gaucher disease (occurs when a certain lipid, glucosylceramide, accumulates causing spleen or liver enlargement and even severe brain damage), among others. (inquirer.net)
- Cerezyme is a prescription medication used to treat Type 1 Gaucher disease, also known as glucocerebrosidase deficiency, which occurs when a lipid called glucosylceramide accumulates in the bone marrow, lungs, spleen, liver and sometimes the brain. (rxwiki.com)
Glycolipid3
- Inhibiting glycolipid biosynthesis by blocking glucosylceramide synthase has been proposed to reverse drug resistance in MDR cells by causing an increased accumulation of proapoptotic ceramide during treatment of cells with cytotoxic drugs. (ox.ac.uk)
- Glucosylceramide, the accumulated glycolipid, is primarily derived from the phagocytosis and degradation of senescent leukocytes and erythrocyte membranes. (medscape.com)
- Glucosylceramide, the accumulated glycolipid, is primarily derived from the phagocytosis and degradation of senescent leukocytes and, to a lesser extent, from erythrocyte membranes. (medscape.com)
Gaucher1
- The oral glucosylceramide (glucocerebroside) synthase inhibitor eliglustat, approved by the FDA for treatment of Gaucher disease type 1 (GD1) in August 2014, has proven as effective as intravenous enzyme replacement therapy with imiglucerase. (medscape.com)
Glucocerebrosidase4
- Mutations in the gene coding for glucocerebrosidase (GBA), which metabolizes glucosylceramide into glucose and ceramide, is the most common genetic risk factor for sporadic PD. (mdsabstracts.org)
- Background:Mutations in the gene coding for glucocerebrosidase (GBA), which metabolizes glucosylceramide (a monohexosylceramide) into glucose and ceramide, is the most common genetic risk factor for sporadic Parkinson's disease (PD). (johnshopkins.edu)
- Imiglucerase is one of three enzymes that can be given intravenously to supplement the patient's glucocerebrosidase and break down accumulated glucosylceramide. (medscape.com)
- It is due to mutations in the glucocerebrosidase gene (GBA) that catalyses the hydrolysis of glucosylceramide (GlcCer). (fundacionareces.es)
Enzyme3
- Glucosylceramide beta-1,4-galactosyltransferase (EC 2.4.1.274, lactosylceramide synthase, uridine diphosphate-galactose:glucosyl ceramide beta 1-4 galactosyltransferase, UDP-Gal:glucosylceramide beta1->4galactosyltransferase, GalT-2, UDP-galactose:beta-D-glucosyl-(1 1)-ceramide beta-1,4-galactosyltransferase) is an enzyme with systematic name UDP-alpha-D-galactose:beta-D-glucosyl-(1 1)-ceramide 4-beta-D-galactosyltransferase. (wikipedia.org)
- These agents inhibit the enzyme glucosylceramide synthase, the initial enzyme in a series of reactions that result in the synthesis of most glycosphingolipids, including glucocerebroside. (medscape.com)
- This product is a glucosylceramide synthase inhibitor, an enzyme that is essential for the synthesis of a very large number of different glycolipids that are found in many organisms.1 PDMP has four possible isomers due to its two chiral centers (D- threo , L- threo , D- erythro , and L- erythro ). (matreya.com)
Ceramides4
- To determine whether plasma ceramides, glucosylceramides, and their ratios predict cognitive decline among cognitively normal Parkinson's disease (PD) patients. (mdsabstracts.org)
- Plasma ceramides and glucosylceramides were determined by LC/ESI/MS/MS. Linear mixed models were used to assess the association between baseline plasma ceramides and glucosylceramides, their ratios, and 12-month change in cognitive performance adjusting for age, sex, education, and disease duration. (mdsabstracts.org)
- Many of the ceramides and glucosylceramides were associated with greater cognitive decline in tests of attention and psychomotor speed, but the ratios were most predictive. (mdsabstracts.org)
- The D- threo isomer has been shown to be the active glucosylceramide synthase inhibitor.2 Due to PDMP's ability to inhibit the joining of ceramides with carbohydrates there can be an accumulation of ceramide in the cells and this can lead to apoptosis. (matreya.com)
Phosphatidylethanolamine1
- In a human gastric carcinoma cell line (EPG85-257) overexpressing MDR1, outward transport of phosphatidylcholine, phosphatidylethanolamine, glucosylceramide and sphingomyelin analogs via MDR1 Pgp was confirmed using fluorescence spectroscopy. (hu-berlin.de)
Lysosomal1
- 2021 ) A novel glucosylceramide synthase inhibitor attenuates alpha synuclein pathology and lysosomal dysfunction in preclinical models of synucleinopathy. (neurotree.org)
Gangliosides1
- It is phosphorylated by ceramide kinase (CK) to form ceramide-1-phosphate or it can be glycosylated by glucosylceramide synthase to form glycosphingolipids (cerebrosides, globosides, gangliosides). (frontiersin.org)
Accumulation1
- The resulting deficit in GCase activity leads to accumulation of the cellular fats glucosylceramide and glucosylsphingosine. (michaeljfox.org)
Structural1
- Dive into the research topics of 'Structural determination of glucosylceramides isolated from marine sponge by fast atom bombardment collision-induced dissociation linked scan at constant B/E'. Together they form a unique fingerprint. (ewha.ac.kr)
Reduction1
- SRT works via global reduction of glucosylceramide synthase and has been shown to yield outcomes similar to those of ERT in adults. (medscape.com)
Production1
- Glucosylceramide production maintains colon integrity in response to Bacteroides fragilis toxin-induced colon epithelial cell signaling. (bvsalud.org)
Therapy2
- Evaluation, Medical Therapy, and Course of Adult Persistent Hyperinsulinemic Hypoglycemia After Roux-en-Y Gastric Bypass Surgery: A Case Series. (umassmed.edu)
- An oral glucosylceramide inhibitor is an alternate efficacious therapy. (medscape.com)
Inhibitor7
- Eliglustat is a specific inhibitor of glucosylceramide synthase, thereby reducing production of glucosylceramide. (medscape.com)
- This glucosylceramide analogue acts as an inhibitor of glucosylceramide synthase, a Golgi complex enzyme that catalyzes the formation of glucosylceramide from ceramide and UDP-glucose and is the first step in the formation of glucocerebroside-based glycosphingolipids. (nih.gov)
- YARGESA is a glucosylceramide synthase inhibitor indicated as monotherapy for treatment of adult patients with mild/moderate type 1 Gaucher disease for whom enzyme replacement therapy is not a therapeutic option ( 1.1 ). (nih.gov)
- We used a potent inhibitor of glucosylceramide synthase to test whether substrate deprivation could lower globotriaosylceramide levels in α-galactosidase A (α-gal A) knockout mice, a model of Fabry disease. (jci.org)
- Complications observed with another glucosylceramide synthase inhibitor, N-butyldeoxynojirimycin, including weight loss and acellularity of lymphatic organs, were not observed with D-t-EtDO-P4. (jci.org)
- CERDELGA (eliglustat) capsules contain eliglustat tartrate, which is a small molecule inhibitor of glucosylceramide synthase that resembles the ceramide substrate for the enzyme, with the chemical name N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1- yl)propan-2-yl)octanamide (2R,3R)-2,3-dihydroxysuccinate. (globalrph.com)
- Miglustat N-butyldeoxynojirimycin (NBDNJ), an inhibitor of glucosylceramide synthase, has shown much promise in clinical trials for the treatment of Type I Gaucher disease. (bmj.com)
Glycosphingolipids1
- These agents inhibit the enzyme glucosylceramide synthase, the initial enzyme in a series of reactions that result in the synthesis of most glycosphingolipids, including glucocerebroside. (medscape.com)
Substrate1
- Substrate reduction therapy utilizes imino sugars to inhibit glucosylceramide synthase and potentially abrogate the effects of storage. (ox.ac.uk)
GlcCer2
- Here we demonstrate that kidney glucosylceramide (GlcCer) and ganglioside GM3 levels are higher in human and mouse PKD tissue as compared to normal tissue, regardless of the causative mutation. (nih.gov)
- 2. Structural analysis of glucosylceramides (GlcCer) from species of the Pseudallescheria/Scedosporium complex. (nih.gov)
Accumulates2
- Despite the availability of new and accurate methods to quantitatively measure brain glucosylceramide levels, there is little evidence that glucosylceramide, or its deacetylated derivative, glucosylsphingosine, accumulates in human PD or PD-GBA brain or cerebrospinal fluid. (nih.gov)
- The disease occurs when the lipid glucosylceramide accumulates in the bone marrow, lungs, spleen, liver, and sometimes the brain. (medscape.com)
Glucosylsphingosine1
- C ) Bar graph shows quantitative analysis of total glucosylceramide (GluCer) species and glucosylsphingosine (GlcSph) levels by LC-ESI-MS/MS in flow-sorted microglia cells obtained from Gba wt/wt , Gba lsl/wt , and nGD brains and on immune infiltrates isolated from nGD brain. (elifesciences.org)
Synthesis4
- The results suggest that in the secretory pathway of Vero cells O-glycan initiation and sphingomyelin as well as glucosylceramide synthesis mainly occur beyond the ERGIC in the Golgi apparatus. (unibas.ch)
- Glucosylceramide synthase - encoded by the Ugcg gene - controls the first committed step in the major pathway of glycosphingolipid synthesis. (nih.gov)
- Conditional LoxP-flanked glucosylceramide synthase allele controlling glycosphingolipid synthesis. (nih.gov)
- Synthesis of a novel photoactivatable glucosylceramide cross-linker. (nih.gov)
Golgi1
- Glucosylceramides were detected within lamellar bodies and in trans-Golgi network-like structures of the stratum granulosum. (anaspec.com)
Precursor1
- Glucosylceramide is the precursor to ceramide and is converted into ceramide by enzymes during the process of keratinocyte production. (kindaikagaku.com)
Fungal1
- 4. Characterization of Scedosporium apiospermum glucosylceramides and their involvement in fungal development and macrophage functions. (nih.gov)
Membrane2
- Glucosylceramide modulates membrane traffic along the endocytic pathway. (ox.ac.uk)
- These data demonstrate that both increases and decreases in glucosylceramide levels can dramatically alter the endocytic targeting of lactosylceramide and suggest a role for glucosylceramide in regulation of membrane transport. (ox.ac.uk)
Metabolism1
- A single intraperitoneal injection of D-t-EtDO-P4 resulted in a 55% reduction in renal glucosylceramide, consistent with rapid renal glucosylceramide metabolism. (jci.org)
Increases1
- It has been proven that supply of glucosylceramide to the skin increases the quantity of ceramide in intercellular lipids, thus improving dry skin. (kindaikagaku.com)
Development1
- This work was supported by the Spanish Ministry of Science and Innovation through grant SAF2010-21224, the Spanish AIDS network "Red Temática Cooperativa de Investigación en SIDA" (RD06/0006), "Gala contra la sida: Barcelona 2011," and the Catalan HIV Vaccine Development Program (HIVACAT). (plos.org)
Shown1
- On the other hand, oral administration of b-glucosylceramide (GC) has been shown to alleviate insulin resistance. (termedia.pl)