Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Mutations in transporter protein shed light on neurodegenerative disorders

07.01.2005


Researchers at Stanford University have made new discoveries that shed light on two inherited neurodegenerative disorders that are caused by inability of the body to transport sialic acid out of cellular compartments. The findings focus on how different mutations in one transporter molecule can cause a wide spectrum of symptoms in Salla Disease and infantile sialic acid storage disease (ISSD).



The research appears as the "Paper of the Week" in the January 14 issue of the Journal of Biological Chemistry, an American Society for Biochemistry and Molecular Biology journal.

The free sialic acid storage diseases are a range of rare, autosomal recessive, neurodegenerative disorders that result from the accumulation of sialic acid within lysosomes. There are two forms of the disease--Salla Disease, the milder form, and the more severe infantile sialic acid storage disease (ISSD). "Clinically, these diseases consist of a spectrum," notes Dr. Richard J. Reimer of Stanford University. "In the severe phenotype infants are born with dysmorphic features, enlarged internal organs and die within a few months. With the milder disease the affected individuals have physical and mental developmental delay, but can live to adulthood."


In Salla Disease and ISSD, the amino sugar sialic acid accumulates in lysosomes, the cellular compartments that are responsible for degrading macromolecules. "Sialic acid is part of a number of proteins and normally it is removed from proteins as they are degraded in lysosomes," explains Dr. Reimer. "The free sialic acid is then released into the cytoplasm of the cell so that it can be reincorporated in to newly synthesized proteins. In Salla Disease and ISSD, the sialic acid is removed from the protein, but it is not released from the lysosome."

Genetic studies have shown that mutations in a single gene encoding a protein called sialin are responsible for both diseases. "The milder form is associated with a single mutation and is most common in a region in northern Finland," says Dr. Reimer. "The more severe form does not appear to have a regional or ethnic predilection and can be caused by any of several different mutations. To date a total of 18 mutations have been identified in addition to the Finnish mutation."

To better understand how mutations in sialin cause the two diseases, Dr. Reimer and his colleagues at Stanford altered part of the sialin molecule, causing it to be expressed on the surface of cells rather than inside lysosomes. In doing this, the researchers were able to easily compare the sialic acid transport ability of normal versus mutated versions of sialin. Using this approach, they proved that sialin is responsible for transporting sialic acid out of the lysosome.

Dr. Reimer and his colleagues also evaluated the impact of sialin’s identified mutations on sialic acid export and discovered a direct correlation between the degree of transport activity lost and the severity of the clinical phenotype. "In the more common and milder form of the disease we found that the mutant proteins work, but not as well. Our findings suggest that for the milder form of the disease a functional protein is still produced, but with reduced activity. From the work of others we know that carriers are asymptomatic even with a 50 percent reduction in sialic acid transport activity. This suggests that for the milder form of the disease increasing the level of expression or stability of the protein could be one way to treat the disease," concludes Dr. Reimer.

Nicole Kresge | EurekAlert!
Further information:
http://www.asbmb.org
http://www.jbc.org

More articles from Life Sciences:

nachricht Fine organic particles in the atmosphere are more often solid glass beads than liquid oil droplets
21.04.2017 | Max-Planck-Institut für Chemie

nachricht Study overturns seminal research about the developing nervous system
21.04.2017 | University of California - Los Angeles Health Sciences

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

Im Focus: Quantum-physical Model System

Computer-assisted methods aid Heidelberg physicists in reproducing experiment with ultracold atoms

Two researchers at Heidelberg University have developed a model system that enables a better understanding of the processes in a quantum-physical experiment...

Im Focus: Glacier bacteria’s contribution to carbon cycling

Glaciers might seem rather inhospitable environments. However, they are home to a diverse and vibrant microbial community. It’s becoming increasingly clear that they play a bigger role in the carbon cycle than previously thought.

A new study, now published in the journal Nature Geoscience, shows how microbial communities in melting glaciers contribute to the Earth’s carbon cycle, a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

New quantum liquid crystals may play role in future of computers

21.04.2017 | Physics and Astronomy

A promising target for kidney fibrosis

21.04.2017 | Health and Medicine

Light rays from a supernova bent by the curvature of space-time around a galaxy

21.04.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>