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 Researchers identify cause of hereditary skeletal muscle disorder
22.02.2017 | Klinikum der Universität München

nachricht Second cause of hidden hearing loss identified
20.02.2017 | Michigan Medicine - University of Michigan

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: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Microhotplates for a smart gas sensor

22.02.2017 | Power and Electrical Engineering

Scientists unlock ability to generate new sensory hair cells

22.02.2017 | Life Sciences

Prediction: More gas-giants will be found orbiting Sun-like stars

22.02.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>