Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Study points to molecular origin of neurodegenerative disorders, including Huntington’s disease

26.09.2005


New research from the University of North Carolina at Chapel Hill School of Medicine points to the possible molecular origin of at least nine human diseases of nervous system degeneration.



The findings are currently in PLoS Computational Biology, an open-access journal published by the Public Library of Science (PloS) in partnership with the International Society for Computational Biology.

These neurodegenerative diseases, including Huntington’s disease, share an abnormal deposit of proteins inside nerve cells. This deposition of protein results from a kind of genetic stutter within the cell’s nucleus asking for multiple copies of the amino acid glutamine, a building block of protein structure. These disorders are collectively known as polyglutamine diseases. Along with Huntington’s, these diseases include spinobulbar muscular atrophy; spinocerebellar ataxia types 1, 2, 3, 6, 7 and 17; and dentatorubral-pallidoluysian atrophy, or Haw River Syndrome.


Haw River Syndrome is a genetic brain disorder first identified in 1998 in five generations of a family having ancestors born in Haw River, N.C. The disorder begins in adolescence (between ages 15 and 30 years) and is characterized by progressive and widespread damage to brain function, leading to loss of coordination, seizures, paranoid delusions, dementia and death within 15 to 20 years.

Scientists are uncertain if protein deposition causes nerve cells to deteriorate and die. However, studies show that the greater the number of glutamine repeats in a protein above a certain threshold, the earlier the onset of disease and the more severe the symptoms. This result suggests that abnormally long glutamine tracts render their host protein toxic to nerve cells.

"Polyglutamine expansion greater than 35 to 40 repeats is definitely a key player in disease etiology and, perhaps, cell death," said Dr. Nikolay V. Dokholyan, assistant professor of biochemistry and biophysics at UNC.

In their new study, Dokholyan and UNC co-authors sought to determine why a correlation exists between polyglutamine expansion length and nerve cell death, or disease. They hypothesized that expansion of glutamines results in alternative structures forming within the protein that compete with its normal structure and function.

"As a result, the protein cannot function properly and, possibly, aggregates," Dokholyan said. In other words, an abnormally long sequence of glutamines might take on a shape that prevents the host protein from "folding" or coiling into its functional three-dimensional shape. All protein molecules are simple unbranched chains of amino acids; proper folding into an intricate shape enables these molecules to perform their biological function.

Researchers used computer simulations to mimic polyglutamine behavior. The UNC study showed that when the number of glutamine repeats exceeds a critical value, the glutamines tend to take on a specific shape in the protein called a beta helix. Moreover, the tendency to form a beta helix increases as glutamine tract length becomes longer.

"In our simulations, when the length is 25 glutamines, no beta helix forms. At 45, a large majority show beta helix formation," Dokholyan said. "And it appears that 37 glutamines marks a transition, as only a small number of beta helices are formed."

Dokholyan said one of his team’s goals is to find a way to inhibit the formation of protein aggregates.

"If we understand the mechanism and the structure, it may become possible to develop ways, including new small molecule drugs, that would interfere with the process of aggregation.

"Our philosophy in general has been that many diseases have underlying molecular etiology. And if something goes wrong at the organism level, it also goes wrong at the molecular level. We try to understand the dynamics and the change in structure that occurs in these molecules with the hope of uncovering their toxicity to the cell."

Co-authors with Dokholyan are graduate student Sagar D. Khare, postdoctoral researcher Dr. Feng Ding and Kenneth N. Gwanmesia, undergraduate student in physics and pre-engineering at Delaware State University.

L.H. Lang | EurekAlert!
Further information:
http://www.med.unc.edu

More articles from Studies and Analyses:

nachricht The Great Unknown: Risk-Taking Behavior in Adolescents
19.01.2017 | Max-Planck-Institut für Bildungsforschung

nachricht A sudden drop in outdoor temperature increases the risk of respiratory infections
11.01.2017 | University of Gothenburg

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

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

Im Focus: Scientists spin artificial silk from whey protein

X-ray study throws light on key process for production

A Swedish-German team of researchers has cleared up a key process for the artificial production of silk. With the help of the intense X-rays from DESY's...

Im Focus: Quantum optical sensor for the first time tested in space – with a laser system from Berlin

For the first time ever, a cloud of ultra-cold atoms has been successfully created in space on board of a sounding rocket. The MAIUS mission demonstrates that quantum optical sensors can be operated even in harsh environments like space – a prerequi-site for finding answers to the most challenging questions of fundamental physics and an important innovation driver for everyday applications.

According to Albert Einstein's Equivalence Principle, all bodies are accelerated at the same rate by the Earth's gravity, regardless of their properties. This...

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Breaking the optical bandwidth record of stable pulsed lasers

24.01.2017 | Physics and Astronomy

Choreographing the microRNA-target dance

24.01.2017 | Life Sciences

Spanish scientists create a 3-D bioprinter to print human skin

24.01.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>