scholarly journals A New Brain‐Penetrant Glucosylceramide Synthase Inhibitor as Potential Therapeutics for Gaucher Disease

2021 ◽  
Author(s):  
Takahiro Fujii ◽  
Yuta Tanaka ◽  
Hideyuki Oki ◽  
Sho Sato ◽  
Sachio Shibata ◽  
...  
Keyword(s):  
Gaucher Disease ◽  
Glucosylceramide Synthase ◽  
Synthase Inhibitor ◽  
Potential Therapeutics

scholarly journals Systemic Delivery of a Glucosylceramide Synthase Inhibitor Reduces CNS Substrates and Increases Lifespan in a Mouse Model of Type 2 Gaucher Disease

PLoS ONE ◽  
2012 ◽  
Vol 7 (8) ◽  
pp. e43310 ◽  
Author(s):  
Mario A. Cabrera-Salazar ◽  
Matthew DeRiso ◽  
Scott D. Bercury ◽  
Lingyun Li ◽  
John T. Lydon ◽  
...  
Keyword(s):  
Mouse Model ◽  
Gaucher Disease ◽  
Systemic Delivery ◽  
Glucosylceramide Synthase ◽  
Synthase Inhibitor

scholarly journals Glucosylceramide Synthase Inhibitor Inhibits the Action of Nerve Growth Factor in PC12 Cells

1998 ◽  
Vol 273 (40) ◽  
pp. 26001-26007 ◽  
Author(s):  
Tatsuro Mutoh ◽  
Akira Tokuda ◽  
Jin-ichi Inokuchi ◽  
Masaru Kuriyama
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Pc12 Cells ◽  
Glucosylceramide Synthase ◽  
Nerve Growth ◽  
Synthase Inhibitor

Correlation Between Glucosylceramide Synthase Gene Polymorphism and Severity Score Index in Type 1 Gaucher Disease

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4644-4644
Author(s):  
Pilar Alfonso ◽  
Silvia Navarro ◽  
Pilar Medina ◽  
Pilar Irun ◽  
Pilar Giraldo ◽  
...  
Keyword(s):  
Severity Score ◽  
Gaucher Disease ◽  
Clinical Severity ◽  
Mobility Shift ◽  
Glucosylceramide Synthase ◽  
In Silico Studies ◽  
Mobility Shift Assay ◽  
Cellular Dysfunction ◽  
Severity Score Index ◽  
Score Index

Abstract Background: Gaucher disease (GD), caused by a deficiency of the glucocerebrosidase (GC) enzyme, is characterized by the accumulation of glucosylceramide (GlcCer) within lysosomes, resulting in cellular dysfunction and damage. GlcCer is catalyzed by the glucosylceramide synthase (GCS), also known as UDP-glucose ceramide glucosyltransferase, (UGCG), EC 2.4.1.80, first enzyme in glycosphingolipids biosynthesis. Mutations in the glucocerebrosidase (GBA) gene are required to cause GD, but other factors play an important role. Aims: GCS gene is a logical candidate to hypothesize that its variability could be involved in clinical severity. Patients and methods: We have analyzed GCS variants (g.(−295)C>T, g.(−222)ins10, g.148A>G, g.166A>T, g.25510C>G, g.29312A>G and g.34991A>G) in a group of 80 [N370S]+[L444P] heterozygous and 23 N370S homozygous patients. Results: were related with severity score index (SSI). g.(−295)C>T and g.166A>T SNPs were in complete linkage disequilibrium. In the N370S homozygous, carriers of g.(−222)ins10 have higher SSI than non carriers (6.6 vs 2.4, p<0.004). Patient carriers of the A-allele for SNP g.148A>G had higher SSI than the G-allele carriers (6.7 vs 1.5, p<0.001, for [N370S]+[L444P] heterozygous and 4.3 vs 1.7, p<0.001, for [N370S] homozygous). “In silico” studies and electrophoretic mobility shift assay (EMSA) indicate that 10bp insertion at the promoter region generates a new ETF binding site and the g.148a>g variant at intron 1 changes the affinity for the transcription factor AP-2. GlcCer were elevated in patient carriers of one mutated allele of these two variants. Conclusion: our results suggest that the genetic GCS variants could influence in the development and progression of GD severity.

scholarly journals A Glucosylceramide Synthase Inhibitor Protects Rats Against the Cytotoxic Effects of Shiga Toxin 2

2011 ◽  
Vol 69 (5 Part 1) ◽  
pp. 390-394 ◽  
Author(s):  
CLAUDIA SILBERSTEIN ◽  
MARÍA S. LUCERO ◽  
ELSA ZOTTA ◽  
DIANE P. COPELAND ◽  
LI LINGYUN ◽  
...  
Keyword(s):  
Shiga Toxin ◽  
Glucosylceramide Synthase ◽  
Cytotoxic Effects ◽  
Shiga Toxin 2 ◽  
Synthase Inhibitor

Erratum to “Design and synthesis of iminosugar-based inhibitors of glucosylceramide synthase: the search for new therapeutic agents against Gaucher disease”

2005 ◽  
Vol 16 (13) ◽  
pp. 2349
Author(s):  
Charlotte Boucheron ◽  
Valérie Desvergnes ◽  
Philippe Compain ◽  
Olivier R. Martin ◽  
Alon Lavi ◽  
...  
Keyword(s):  
Gaucher Disease ◽  
Therapeutic Agents ◽  
Glucosylceramide Synthase ◽  
Design And Synthesis
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