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Printable Handouts
Navigable Slide Index
- Introduction
- Importance of GCase and its role in disease
- Target for molecular therapies
- GCase structure and function
- GBA1 locus
- Chromosome 1 location of GBA1
- GBA1 and pseudo-GBA1 region
- GBA1 fine structure and exonic promoter elements
- GBA1 and pseudo-GBA1 proximity and structure
- GC synthetic and degradative pathways
- Cellular synthesis and degradation of GC
- Enzymology and cell biology of GCase
- GCase synthesis and lysosomal targeting (1)
- GCase synthesis and lysosomal targeting (2)
- GCase synthesis in cells
- GCase post-translational modifications
- Co-localization of LAMP-2 and GCase
- Role of LIMP-2 in trafficking of GCase to lysosome
- GCase enzymology
- Glycosphingolipid degradative pathway scheme
- Basic properties of GCase
- Basic parameters of GCase
- The crystal structure of GCase
- The GCase catalytic mechanism
- Prosaposin structure
- GCase and saposin C
- Saposin C structure
- The lysosomal inner membrane and GCase activity
- GCase and Gaucher disease
- Macrophages
- GCase deficiency creates characteristic cell type
- Pathogenesis of Gaucher disease
- Gaucher disease: classical clinical variants
- GCase gene and Gaucher disease mutant alleles
- Gaucher disease associated "recombinant alleles"
- Genotype/phenotype and molecular correlations
- The crystal structure of GCase in Gaucher disease
- Genotype/Phenotype and residual activity levels
- Therapies for Gaucher disease
- Macrophage mannose receptor
- Gaucher disease enzyme therapy
- GD1 enzyme therapy animation
- Mechanisms of pharmacological chaperone effects
- Summary (1)
- Summary (2)
Topics Covered
- Properties of GCase: structure and function
- Enzymology and cell biology of GCase
- Requirements for GCase activity
- GCase and its role in Gaucher disease
- Genotype/Phenotype and molecular correlations
- Therapies for Gaucher disease (enzymes, genes, chaperones)
Talk Citation
Grabowski, G. (2016, July 27). Acid beta-glucosidase/glucocerebrosidase (GCase) [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved October 7, 2024, from https://doi.org/10.69645/VKOQ7295.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Gregory Grabowski has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
Acid beta-glucosidase/glucocerebrosidase (GCase)
A selection of talks on Clinical Practice
Transcript
Please wait while the transcript is being prepared...
0:00
Welcome to a presentation on Acid β-Glucosidase or Glucocerebrosidase.
Throughout this talk, we'll refer to this as GCase.
My name is Gregory A. Grabowski.
I'm a Physician, Professor Emeritus in
the Department of Pediatrics and in the Division of
Human Genetics at Cincinnati Children's Hospital Medical Center,
and I am Chief Scientific Officer at Kiniksa Pharmaceuticals,
Ltd in Wellesley, Massachusetts.
0:29
We will first deal with the importance of GCase and its role in disease.
GCase degrades glucosylceramide, which is
an important glycosphingolipid in development and within all cell membranes,
the precursor to ceramide and is
a critical signaling lipid in the regulation of apoptosis and inflammation.
Defective GCase causes a disease called Gaucher disease.
This is a common lysosomal storage diseases and GCase is a lysosomal hydrolase.
It has been a prototype for molecular therapies.
1:08
GCase has become a target for molecular therapies and, in particular,
the development of enzyme therapy by supplying wild type functional GCase by
intravenous administration has improved the lives of
patients with Gaucher disease over the past 15 years.
Gene therapy has also been used in exploratory ways for
the expression of the GCase gene in selected cell types,
in particular, in stem cells of
the hematopoietic origin since the disease relates to the macrophage system.
In addition, expression at high levels in other organs such as the liver could be
used as an organoid approach to the therapy of Gaucher disease.
Finally, it has become a target for the development of a new method of
treatment with significant potential termed chaperone therapy in
which the endogenous defective GCase activity is
enhanced by use of small molecules to re-conform the defective enzyme.