Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Research suggests cause of neurodegeneration in Huntington’s disease

31.05.2006


The severe neurodegeneration associated with HuntingtonÕs disease may result from molecular mutations that block the transport of nutrients within cells. Findings from the Emory University School of Medicine indicate that the mutant huntingtin protein limits the efforts of the huntingtin-associated protein-1 (HAP1) to provide nutrients to growing neurons, or neurites. Without those nutrients, neurites fail to develop and mature neurons degenerate.



Huntington’s disease was first identified more than 125 years ago, and often inhibits speech, movement, reasoning and memory. The result of an abnormal Huntington gene, the hereditary disorder is estimated to affect one out of every 10,000 people. Though some current pharmacological treatments do address symptoms, scientists have been unable to stop the disease’s progression.

However, scientists at Emory are making headway in the search for a cure. The findings that appear in the May 31 issue of the Journal of Neuroscience are the latest of more than a decade of Huntington’s disease-related discoveries led by Xiao-Jiang Li, PhD, professor of human genetics at Emory University School of Medicine.


Juan Rong, doctoral student in the neuroscience graduate program at the Emory University School of Medicine, is the lead author of the article. The senior author, Dr. Li, first discovered the protein HAP1 as a postdoctoral fellow in 1995. In previous articles, he has identified the importance of HAP1 to the normal functioning of the hypothalamus, a region of the brain that acts as a central switchboard to regulate feeding and other body functions. Earlier this year, Dr. Li’s group published an article identifying HAP1Õs role connecting insulin to the hypothalamus in the journal Nature Medicine.

"This protein is very important," says Dr. Li. "When an animal does not have HAP1 it dies after birth. Certainly, it’s essential for differentiation and survival of some neurons in the brain."

In this latest paper, Dr. Li, Ms. Rong, and their colleagues used cellular models to show that HAP1 normally links to transport proteins, including the growth factor receptor tyrosine kinase (TrkA), in growing neurites. HAP1 protects TrkA from degrading, ensuring the neurites continue to develop. This trafficking function is regulated by the addition of phosphate and oxygen to the HAP1 protein, a process known as phosphorylation.

However, when mutant huntingtin is present, the Emory researchers have found that this disease protein stops HAP1 from fulfilling its trafficking function. HAP1 cannot prevent the degradation of TrkA. The insufficient amount of TrkA cannot maintain the normal function of nerve terminals.

Although the discovery that HAP1 works as a transporter and plays a crucial role in neuronal function was obtained from cell models, it will assist scientists as they continue to look for a cure for Huntington’s disease. Dr. Li’s current experiments involve selective HAP1 deletions from neurons in animal models, and his results are sure to offer relevant clues to the mechanisms behind HuntingtonÕs disease.

Says Dr. Li, "If we can find the pathogenesis for Huntington’s disease, or if we know how the mutant huntingtin affects the transporting inside cells, maybe then we can find some effective treatment to prevent this kind of defect."

Research into other neurodegenerative disorders may also benefit from a thorough understanding of HAP1. "This work also has implications for understanding the normal physiological processing for neuronal functioning," says Dr. Li.

Holly Korschun | EurekAlert!
Further information:
http://www.emory.edu

More articles from Health and Medicine:

nachricht Tracking movement of immune cells identifies key first steps in inflammatory arthritis
23.01.2017 | Massachusetts General Hospital

nachricht Team discovers how bacteria exploit a chink in the body's armor
20.01.2017 | University of Illinois at Urbana-Champaign

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

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...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

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

Tracking movement of immune cells identifies key first steps in inflammatory arthritis

23.01.2017 | Health and Medicine

Electrocatalysis can advance green transition

23.01.2017 | Physics and Astronomy

New technology for mass-production of complex molded composite components

23.01.2017 | Process Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>