Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH MEDIA
GLOBETECH PUBLISHING LLC
GLOBETECH PUBLISHING LLC

Enzyme Deficiency Improves Clinical Picture in Mouse Model of Gaucher's Disease

By BiotechDaily International staff writers
Posted on 10 Feb 2014
Image: Elevation of RIPK3 in nuclei of neurons (red; arrows) from neuronopathic Gaucher's disease mice (Photo courtesy of Dr. Anthony Futerman, Weizmann Institute of Science).
Image: Elevation of RIPK3 in nuclei of neurons (red; arrows) from neuronopathic Gaucher's disease mice (Photo courtesy of Dr. Anthony Futerman, Weizmann Institute of Science).
Blocking the activity of a specific enzyme reversed the clinical symptoms of Gaucher's disease (GD) in a mouse model of this hereditary lipid storage disease.

GD is a hereditary disease caused by a recessive mutation in a gene located on chromosome 1 that causes a deficiency of the enzyme glucocerebrosidase. This enzyme acts on the fatty acid glucosylceramide, and when the enzyme is defective, glucosylceramide accumulates, particularly in white blood cells, most often macrophages. Glucosylceramide can also collect in the spleen, liver, kidneys, lungs, brain, and bone marrow. Clinical manifestations may include enlarged spleen and liver, liver malfunction, skeletal disorders and bone lesions that may be painful, severe neurological complications, swelling of lymph nodes, distended abdomen, a brownish tint to the skin, anemia, low blood platelets and yellow fatty deposits on the white of the eye.

Investigators at the Weizmann Institute of Science (Rehovot, Israel) examined the role of the enzyme Ripk3 (receptor-interacting serine-threonine-protein kinase 3) in GD. Ripk3, the product of the RIPK3 gene, is predominantly localized to the cytoplasm, and can undergo nucleocytoplasmic shuttling dependent on novel nuclear localization and export signals. It is a component of the tumor necrosis factor (TNF) receptor-I signaling complex, and can induce apoptosis and weakly activate the transcription factor NF-kappaB.

To study the relationship between Ripk3 and GD the investigators used a GD mouse model that included animals with and without active Ripk3. Results published in the January 19, 2014, online edition of the journal Nature Medicine revealed that Ripk3 deficiency substantially improved the clinical course of GD in the mice, with increased survival and motor coordination and salutary effects on cerebral as well as hepatic injury. Furthermore, the lifespan of these mice was remarkably increased, from approximately 35 days to more than 170 days.

“If successful, the new target could be used as either a complementary or alternative therapy for Gaucher's disease, and with RIPK3 proving to be a "hot" cellular pathway in various pathologies, these results may also have implications in other neurodegenerative diseases, including related diseases such as Krabbe disease, and potentially other devastating brain diseases,” said senior author Dr. Anthony Futerman, professor of biological chemistry at the Weizmann Institute of Science.

Related Links:

Weizmann Institute of Science
 


Channels

Drug Discovery

view channel
Image: Molecular model of the protein Saposin C (Photo courtesy of Wikimedia Commons).

Nanovesicles Kill Human Lung Cancer Cells in Culture and in a Mouse Xenograft Model

Nanovesicles assembled from the protein Saposin C (SapC) and the phospholipid dioleoylphosphatidylserine (DOPS) were shown to be potent inhibitors of lung cancer cells in culture and in a mouse xenograft model.... Read more

Biochemistry

view channel

Possible New Target Found for Treating Brain Inflammation

Scientists have identified an enzyme that produces a class of inflammatory lipid molecules in the brain. Abnormally high levels of these molecules appear to cause a rare inherited eurodegenerative disorder, and that disorder now may be treatable if researchers can develop suitable drug candidates that suppress this enzyme.... Read more

Lab Technologies

view channel
Image: The FLUOVIEW FVMPE-RS Gantry microscope (Photo courtesy of Olympus).

New Multiphoton Laser Scanning Microscope Configurations Expand Research Potential

Two new configurations of a state-of-the-art multiphoton laser scanning microscope extend the usefulness of the instrument for examining rapidly occurring biological events and for obtaining images from... Read more

Business

view channel

Roche Acquires Signature Diagnostics to Advance Translational Research

Roche (Basel, Switzerland) will advance translational research for next generation sequencing (NGS) diagnostics by leveraging the unique expertise of Signature Diagnostics AG (Potsdam, Germany) in biobanks and development of novel NGS diagnostic assays. Signature Diagnostics is a privately held translational oncology... Read more
 
Copyright © 2000-2015 Globetech Media. All rights reserved.