Beta-glucosidaseCeramideAccumulation of glucosylceramideGlcCerMutationsGlucosylceramidaseGCaseGeneGlucosylsphingosineDeficiency of glucocerebrosidaseGaucher DiseaseAcidSynthase inhibitorAccumulatesGlucoseMacrophagesGBA1RecombinantLipidHydrolaseLysosomesMutationCell membraneGaucher's DiseaseParkinson's DiseaseSubstrateIntravenouslyDiseaseEliminateDiagnosisActivityReductionDisorderPrimarilyTherapyReplacement
Beta-glucosidase4
- The disorder results from the deficiency of a specific lysosomal hydrolase, glucocerebrosidase (also termed acid beta-glucosidase, glucosylceramidase). (medscape.com)
- The enzyme lysosomal glucocerebrosidase (beta-glucosidase, glucosylceramidase)catalyzes the breakdown of a cell membrane constituent of red and white blood cells, called glucosylceramide. (tu-muenchen.de)
- The cause of Gaucher disease is a recessive mutation in a houskeeping gene lysosomal glucocerebrosidase (beta-glucosidase, glucosylceramidase) on chromosome 1 (1q21). (tu-muenchen.de)
- GD is caused by a genetic mutation of the gene that codes for a lysosomal enzyme called 'b-glucocerebrosidase' (acid beta-glucosidase or GCase). (gaucherdiseaseplatform.org)
Ceramide7
- The activity of lysosomal acid β-glucocerebrosidase (AGC, EC 3.2.1.45), which hydrolyzes the O-glycosidic linkage between d-glucose and ceramide of glucosylceramide (GlcCer), is a marker for the diagnosis of Gaucher disease because the disease is caused by dysfunction of AGC due to mutations in the gene. (elsevierpure.com)
- In the lysosome the glucocerebrosidase cleaves the glucosylceramide into ceramide and glucose. (tu-muenchen.de)
- 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)
- 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)
- Glucocerebrosidase normally hydrolyzes glucocerebroside to glucose and ceramide. (msdmanuals.com)
- 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)
Accumulation of glucosylceramide3
- GD is the most prevalent lysosomal storage disease, characterized by the accumulation of glucosylceramide in the reticuloendothelial system. (lifesciencesexpo.com)
- Mutations in this gene lead to reduced GCase activity, accumulation of glucosylceramide and glucosylsphingosine, and development of Gaucher disease (GD). (tau.ac.il)
- Gaucher's disease is a rare Lysosomal Storage Disorder (LSD) caused by the accumulation of glucosylceramide/glucocerebroside. (ejournals.ca)
GlcCer4
- It is due to mutations in the glucocerebrosidase gene (GBA) that catalyses the hydrolysis of glucosylceramide (GlcCer). (fundacionareces.es)
- Human GBA1 encodes lysosomal acid β-glucocerebrosidase (GCase), which hydrolyzes cleavage of the beta-glucosidic linkage of glucosylceramide (GlcCer). (tau.ac.il)
- This study aimed to probe the molecular basis for the anti-inflammatory activity of miglustat by examining specifically the role of GBA2 following the contamination of CF bronchial epithelial cells by synthesis Sparsentan or hydrolysis of complex SLs, such as sphingomyelin (SM) by acid sphingomyelinase (ASM) and glucosylceramide (GlcCer) by glucocerebrosidases [12]. (acusticavisual.net)
- The deficiency of the enzyme causes a toxic accumulation of certain fatty substances such glucosylceramide (GlcCer) and glucosylsphingosine (lyso-GB1) in certain organs, including the spleen, liver and bone. (avrobio.com)
Mutations5
- Mutations in the glucocerebrosidase gene cause Gaucher's disease, a lysosomal storage disease characterized by an accumulation of glucocerebrosides in macrophages that infiltrate many vital organs. (wikipedia.org)
- Mutations in the glucocerebrosidase gene are also associated with Parkinson's disease. (wikipedia.org)
- Mutations in the GBA gene leads to an abnormal production of the enzyme b-glucocerebrosidase. (gaucherdiseaseplatform.org)
- Gaucher's disease (GD), an inherited metabolic disorder caused by mutations in the glucocerebrosidase gene (GBA), is the most common lysosomal storage disease. (ox.ac.uk)
- 7. Beutler E, Demina A, Gelbart T. Glucocerebrosidase mutations in Gaucher disease. (ejournals.ca)
Glucosylceramidase1
- β-Glucocerebrosidase (also called acid β-glucosidase, D-glucosyl-N-acylsphingosine glucohydrolase, or GCase) is an enzyme with glucosylceramidase activity (EC 3.2.1.45) that cleaves by hydrolysis the β-glycosidic linkage of the chemical glucocerebroside, an intermediate in glycolipid metabolism that is abundant in cell membranes (particularly skin cells). (wikipedia.org)
GCase2
- Type 1 GD was the first lysosomal storage disease (LSD) for which enzyme therapy became available, and although infusions of recombinant glucocerebrosidase (GCase) ameliorate the systemic effects of GD, the lack of efficacy for the neurological manifestations, along with the considerable expense and inconvenience of enzyme therapy for patients, renders the search for alternative or complementary therapies paramount. (ox.ac.uk)
- Gaucher disease is a rare genetic disorder resulting from a deficiency of the enzyme glucocerebrosidase, also known as GCase. (avrobio.com)
Gene4
- The GBA gene provides instructions for making an enzyme called beta-glucocerebrosidase. (medlineplus.gov)
- Variants in the GBA gene greatly reduce or eliminate the activity of beta-glucocerebrosidase. (medlineplus.gov)
- Non-lysosomal pathways of degradation also exist and for instance glucosylceramides can be degraded not only from the lysosomal glucocerebrosidase, but also from the non-lysosomal glucocerebrosidase (encoded from the gene) and the cytosolic Klotho-related glucocerebrosidase (encoded from the gene) [26C31]. (e-core.org)
- Normally the GBA gene is involved in giving instructions for the production of b-glucocerebrosidase. (gaucherdiseaseplatform.org)
Glucosylsphingosine2
- The factors that contribute to neurologic involvement in patients with types 2 and 3 disease are still unknown but may be related to the accumulation of a cytotoxic glycolipid, glucosylsphingosine, in the brain due to the severe deficiency of glucocerebrosidase activity or to neuroinflammation. (medscape.com)
- Glucosylceramide and glucosylsphingosine accumulation in the brain leads to massive neuronal loss in patients with neuronopathic GD (nGD) and in nGD mouse models. (ox.ac.uk)
Deficiency of glucocerebrosidase1
- Gaucher disease is caused by a deficiency of glucocerebrosidase (acid-glucosidase), an enzyme that helps break down a cellular membrane sphingolipid called glucocerebroside (glucosylceramide) inside lysosomes. (canbridgepharma.com)
Gaucher Disease4
- 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)
- It works by replacing the enzyme glucocerebrosidase, which people with Gaucher disease do not have enough of. (rxwiki.com)
- 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)
- For more than 25 years, recombinant human glucocerebrosidase enzyme replacement therapy (ERT) has been the standard of care for Gaucher disease, with clinical trials and real-world data demonstrating significant improvement in the major non-neurological signs and symptoms of disease and quality of life. (canbridgepharma.com)
Acid1
- The two aliphatic chains of glucocerebroside may remain associated with the lysosomal bilayer or interact with the activating protein Saposin C. Consistent with other glycoside hydrolases, the mechanism of glucocerebroside hydrolysis by β-glucocerebrosidase involves acid/base catalysis by two glutamic acid residues (E340 and E235) and precedes through a two-step mechanism. (wikipedia.org)
Synthase inhibitor1
- 2021 ) A novel glucosylceramide synthase inhibitor attenuates alpha synuclein pathology and lysosomal dysfunction in preclinical models of synucleinopathy. (neurotree.org)
Accumulates2
- The disease occurs when the lipid glucosylceramide accumulates in the bone marrow, lungs, spleen, liver, and sometimes the brain. (medscape.com)
- In GD, glucocerebroside accumulates in macrophage cells as the enzyme b-glucocerebrosidase (which is located within the lysosomes) fails to effectively break it down. (gaucherdiseaseplatform.org)
Glucose2
- Crystal structures indicate that β-glucocerebrosidase binds the glucose moiety and adjacent O-glycosydic bond of glucocerebroside. (wikipedia.org)
- β-Glucocerebrosidase is specifically and irreversibly inhibited by the glucose analog Conduritol B epoxide. (wikipedia.org)
Macrophages1
- Macrophages which eliminate these cells cannot process glucosylceramide of the cell membranes. (tu-muenchen.de)
GBA11
- 2021 ) Decreased glucocerebrosidase activity and substrate accumulation of glycosphingolipids in a novel GBA1 D409V knock-in mouse model. (neurotree.org)
Recombinant1
- CAN103 is a recombinant human glucocerebrosidase ERT that is being developed to treat GD Types I and III, which are the chronic non-neuronopathic and neuronopathic forms of the disease that constitute the majority of patients. (canbridgepharma.com)
Lipid1
- This allows a macromolecule lipid (fatty substance) called glucocerebroside (also called glucosylceramide, which is a glycosphingolipid) to accumulate within the cells of the body - particularly the liver, spleen, brain (in Type 2 and 3) and bone marrow. (gaucherdiseaseplatform.org)
Hydrolase1
- β-Glucocerebrosidase is a member of the glycoside hydrolase family 30 and consists of three distinct domains (I-III). (wikipedia.org)
Lysosomes1
- CAN103 is delivered intravenously and is intended to supplement the lack of glucocerebrosidase in the lysosomes of GD patients. (canbridgepharma.com)
Mutation1
- It will enrol mild Parkinson's disease patients who are on standard-of-care therapy, irrespective of their glucocerebrosidase (GBA) mutation status. (clinicaltrialsarena.com)
Cell membrane1
- In these immunocells, the lysosomal glucocerebrosidase acts on the fatty acids of the cell membrane. (tu-muenchen.de)
Gaucher's Disease1
- Gaucher's disease, also known as glucocerebrosidase deficiency, is an autosomal recessive disease that affects about 1 in 20,000 live births. (medscape.com)
Parkinson's Disease2
- 2023 ) Pyrazole Ureas as Low Dose, CNS Penetrant Glucosylceramide Synthase Inhibitors for the Treatment of Parkinson's Disease. (neurotree.org)
- To determine whether plasma ceramides, glucosylceramides, and their ratios predict cognitive decline among cognitively normal Parkinson's disease (PD) patients. (mdsabstracts.org)
Substrate1
- In contrast, substrate reduction therapy works by inhibiting glucosylceramide synthase, slowing the production of glucosylceramide. (medscape.com)
Intravenously1
- Imiglucerase is one of three enzymes that can be given intravenously to supplement the patient's glucocerebrosidase and break down accumulated glucosylceramide. (medscape.com)
Disease1
- 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)
Eliminate1
- The combination of RTB101 and sirolimus is expected to trigger autophagy to eliminate protein aggregates in neurons, increasing lysosomal biogenesis and decreasing glucosylceramide (GL1) synthesis. (clinicaltrialsarena.com)
Diagnosis1
- Diagnosis can be confirmed through measurement of glucocerebrosidase activity in peripheral blood leukocytes. (medscape.com)
Activity1
- The activity of AGC is potently inhibited by conduritol B epoxide (CBE), whereas CBE-insensitive nonlysosomal neutral β-glucocerebrosidase (NGC) activities have been found in various vertebrates, including humans. (elsevierpure.com)
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)
Disorder2
- The disorder results from the deficiency of the enzyme glucocerebrosidase. (medscape.com)
- an inherited disorder of metabolism, resulting from glucocerebrosidase deficiency, causing deposition of glucocerebroside and related compounds. (msdmanuals.com)
Primarily2
- 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)
Therapy1
- An oral glucosylceramide inhibitor is an alternate efficacious therapy. (medscape.com)
Replacement1
- Treatment is enzyme replacement with glucocerebrosidase. (msdmanuals.com)