Navigation Links
Discovery of source of glycogen 'manufacturing' errors sheds light on fatal disease

Indiana University scientists have solved a perplexing mystery regarding one of the body's main energy storage molecules, in the process shedding light on a possible route to treatment of a rare but deadly disease in teenagers.

The disease occurs when a genetic mutation causes excessive amounts of phosphate to build up in glycogen. Glycogen is a chain-like molecule the body uses to temporarily store glucose when it's not needed to provide energy for cellular activities. The excess phosphate causes unnatural glycogen structures to appear in the body, including the brain, resulting in progressive neurological problems.

In a paper in the March 2, 2011 issue of the journal Cell Metabolism, a research team led by Peter J. Roach, Ph.D., professor of biochemistry and molecular biology at the IU School of Medicine, has identified where the extra phosphate comes from, and how it is chemically linked to the glycogen molecules. The findings, Dr. Roach said, suggest a possibility for treating the disease stopping the body from producing glycogen.

Lafora disease, named after the Spanish physician who identified it, strikes early in the teen years with epileptic seizures and then other neurological symptoms that grow progressively worse. It is always fatal, usually within 10 years.

"It's a very harrowing disease and there's no treatment right now. It's thankfully rare, but for the families affected it's tragic," said Dr. Roach, Distinguished Professor and a Chancellor's Professor, Indiana University-Purdue University Indianapolis.

The disease is caused by a mutation to one of two genes, one leading to a defective version of a protein called laforin. In previous research, Dr. Roach and his collaborators showed that laforin's role is to remove phosphate residues from glycogen. When the body cannot produce laforin, the phosphate levels in glycogen build up, resulting in Lafora disease.

What had puzzled scientists was the source of the phosphate. The answer, Dr. Roach and his colleagues report in Cell Metabolism, is found in the enzyme that cells normally use to build up the glycogen molecules. When there are extra glucose molecules in the body, such as after a meal, the enzyme, like a tiny molecular machine, hooks the glucose molecules onto the glycogen chain. In the process, phosphates that are attached to the glucose are discarded.

But once every 10,000 cycles or so, a phosphate molecule remains attached when the enzyme hooks the glucose molecule onto the glycogen chain. The job of laforin is to correct for those errors. Without the laforin, phosphates build up and the deadly disease is the result.

Dr. Roach and his colleagues note that animal experiments suggest that a treatment to counteract the laforin mutation could be compounds that would block the production of glycogen. Although a lack of glycogen could have side effects such as greater propensity to develop diabetes they might be acceptable in the face of such a deadly alternative, Dr. Roach said. However, such an approach is only a theoretical possibility at his point, he said.


Contact: Eric Schoch
Indiana University School of Medicine

Related biology news :

1. Chemical equator discovery will aid pollution mapping
2. Sirtris review of sirtuin therapeutics for diseases of aging in Nature Reviews Drug Discovery
3. Groundbreaking discovery may lead to stronger antibiotics
4. Discovery of natural compounds that could slow blood vessel growth
5. Nanoscopic screening process to speed drug discovery
6. FSU researchers discovery leads to $1.5 million grant, potential new treatment of liver fibrosis
7. New $11 million center to speed production of new compounds for drug discovery
8. Discovery of giant roaming deep sea protist provides new perspective on animal evolution
9. New discovery may enhance MRI scans, lead to portable MRI machines
10. Kidney function discovery sheds light on genetic complexity of disease
11. Discovery of new gene associated with diabetes risk suggests link with body clock
Post Your Comments:
Related Image:
Discovery of source of glycogen 'manufacturing' errors sheds light on fatal disease
(Date:5/16/2016)...   EyeLock LLC , a market leader of ... an IoT Center of Excellence in Austin, ... of embedded iris biometric applications. EyeLock,s iris ... security with unmatched biometric accuracy, making it the most ... EyeLock,s platform uses video technology to deliver a fast ...
(Date:5/9/2016)... May 9, 2016 Elevay is ... to expanding freedom for high net worth professionals seeking ... today,s globally connected world, there is still no substitute ... ever duplicate sealing your deal with a firm handshake. ... by taking advantage of citizenship via investment programs like ...
(Date:4/28/2016)... SAN FRANCISCO and BANGALORE, India ... part of EdgeVerve Systems, a product subsidiary of Infosys (NYSE: ... service provider, today announced a global partnership that ... convenient way to use mobile banking and payment services. ... Mobility is a key innovation area for financial services, but ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... ... June 23, 2016 , ... Supplyframe, the ... the Supplyframe Design Lab . Located in Pasadena, Calif., the Design Lab’s ... how hardware projects are designed, built and brought to market. , The Design ...
(Date:6/23/2016)... 2016  Blueprint Bio, a company dedicated to identifying, ... community, has closed its Series A funding round, according ... "We have received a commitment from Forentis Fund ... to meet our current goals," stated Matthew Nunez ... to complete validation on the current projects in our ...
(Date:6/23/2016)... ... June 23, 2016 , ... ... and technical consulting, provides a free webinar on Performing Quality Investigations: ... 2016 at 12pm CT at no charge. , Incomplete investigations are still a ...
(Date:6/22/2016)... , June 22, 2016 Cell Applications, ... allow them to produce up to one billion ... lot within one week. These high-quality, consistent stem ... preparing cells and spend more time doing meaningful, ... a proprietary, high-volume manufacturing process that produces affordable, ...
Breaking Biology Technology: