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 personality factor: How to foster the sharing of research data
06.09.2017 | ZBW – Leibniz-Informationszentrum Wirtschaft

nachricht Europe’s Demographic Future. Where the Regions Are Heading after a Decade of Crises
10.08.2017 | Berlin-Institut für Bevölkerung und Entwicklung

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: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

Im Focus: Fast, convenient & standardized: New lab innovation for automated tissue engineering & drug

MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems Holding GmbH about commercial use of a multi-well tissue plate for automated and reliable tissue engineering & drug testing.

MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems...

Im Focus: Silencing bacteria

HZI researchers pave the way for new agents that render hospital pathogens mute

Pathogenic bacteria are becoming resistant to common antibiotics to an ever increasing degree. One of the most difficult germs is Pseudomonas aeruginosa, a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Molecular Force Sensors

20.09.2017 | Life Sciences

Producing electricity during flight

20.09.2017 | Power and Electrical Engineering

Tiny lasers from a gallery of whispers

20.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>