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)
Accumulation5
The resulting deficit in GCase activity leads to accumulation of two glycosphingolipids, glucosylceramide and glucosylsphingosine. (michaeljfox.org)
It leads to the accumulation of glucosylceramide in cells of mononuclear-macrophage lineage. (anaspec.com)
GD is the most prevalent lysosomal storage disease, characterized by accumulation of glucosylceramide in the reticulo-endothelial system. (proteopedia.org)
GD is characterized by the accumulation of glucosylceramide (GlcCer)-laden macrophages. (nih.gov)
Mutations in GBA reduce glucocerebrosidase (GCase) activity, leading to glucosylceramide accumulation, α-syn aggregation and broad autophagic abnormalities. (biomedcentral.com)
Glucocerebrosidase4
An attractive hypothesis is that the lipid substrate of glucocerebrosidase, glucosylceramide, accumulates in patients with PD with a GBA mutation (PD-GBA). (nih.gov)
Imiglucerase is one of three enzymes that can be given intravenously to supplement the patient's glucocerebrosidase and break down accumulated glucosylceramide. (medscape.com)
In Gaucher disease, the deficient enzyme is glucocerebrosidase, which degrades the fatty molecule glucocerebroside (also known as glucosylceramide), a component of white and red blood cell membranes. (nih.gov)
Glucocerebrosidase (GCase), a lysosomal hydrolase encoded by the GBA gene, is responsible for the metabolism of the glycosphingolipid substrates glucosylceramide (GlcCer) and glucosylsphingosine (GlcSph). (biomedcentral.com)
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)
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)
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)
Glucosylsphingosine2
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)
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)
Substrate1
Substrate reduction therapy utilizes imino sugars to inhibit glucosylceramide synthase and potentially abrogate the effects of storage. (ox.ac.uk)
Enzyme1
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)
Synthase Inhibitors2
The glucosylceramide synthase inhibitors, miglustat and eliglustat, were approved for adults with type 1 Gaucher disease in 2003 and 2014 respectively. (medscape.com)
The disease occurs when the lipid glucosylceramide accumulates in the bone marrow, lungs, spleen, liver, and sometimes the brain. (medscape.com)
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)
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)
Spleen1
C57BL/6 mice treated twice daily for 3 days with D-threo-1-ethylendioxyphenyl-2-palmitoylamino-3-pyrrolidino-propanol (D-t-EtDO-P4) showed a concentration-dependent decrement in glucosylceramide levels in kidney, liver, and spleen. (jci.org)
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)
Precursor1
Glucosylceramide is the precursor to ceramide and is converted into ceramide by enzymes during the process of keratinocyte production. (kindaikagaku.com)
Lysosomal1
Thus, a straightforward association between glucosylceramide levels and the development of PD does not appear valid, necessitating the involvement of other cellular pathways to explain this association, which could involve defects in lysosomal function. (nih.gov)
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)
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)