Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Effects of Huntington’s disease mutation more complex than supposed

23.07.2004


Competing theories about why brain cells die in Huntington’s disease may not be competitors after all, according to a report published July 23, 2004, in the online edition of the Annals of Neurology.



Researchers report finding minor molecular abnormalities of the sort proposed by these different theories in cells throughout the brain and even in the skin. Yet only select groups of cells in a few movement centers of the brain are so vulnerable to these disruptions that they degenerate and die.

The results suggest that therapeutic strategies for Huntington’s--as well as other neurodegenerative diseases such as Alzheimer’s and Parkinson’s--may have to be more complex than previously supposed.


Huntington’s is an inherited, degenerative brain disease marked by movement abnormalities--involuntary, dance-like movements called "chorea" early in the illness and later a gradual loss of the ability to move muscles voluntarily--as well as psychiatric symptoms such as depression and mood swings.

Huntington’s disease is caused by mutations in a single gene. The mutation leads to an abnormal form of the protein called huntingtin, which accumulates into toxic deposits inside nerve cells. Researchers have focused their efforts on understanding why mutant huntingtin accumulates and how it might damage brain cells.

One prominent theory notes that there is a breakdown in the clearance of abnormal proteins in Huntington’s disease. Normally, a cellular "garbage" service called the ubiquitin-proteasome system (UPS) tags defective proteins and disassembles them. In Huntington’s disease, the UPS does not appear to be fully functional, leaving defective proteins like huntingtin to accumulate.

However, researchers have also found other critical defects in the brain cells of Huntington’s patients, including a scarcity of molecules called neurotrophins that nourish brain cells, and problems with mitochondria, the "power plants" that produce energy for cells.

In their study, Ole Isacson, MD, and his colleagues at Harvard University and McLean Hospital explored the relationships between these different cellular processes in different cells inside and outside the brain.

Surprisingly, first author Hyemyung Seo, PhD, and colleagues found that the UPS is not working properly in the skin cells of Huntington’s disease either, yet there is no evidence that this harms the cells. Similarly, the researchers found abnormalities in neurotrophins and mitochondrial operation in many unaffected areas of the brain in Huntington’s disease.

"It appears that only a few select groups of cells in the brain fail to adapt to this combination of problems. The degeneration of these cells leads to Huntington’s disease," said Isacson.

An important implication of the study is that the mutant huntingtin protein does not just have one negative effect on brain cells, but several. This may mean that therapeutic strategies will have to take the form of combinations of drugs that address the different processes.

Mark Cookson, Ph.D, an expert on neurodegenerative disease at the National Institute on Aging in Bethesda, Maryland, believes this study will be of great interest to scientists who study diseases like Alzheimer’s and Parkinson’s, which also feature accumulations of abnormal proteins, problems in UPS "garbage collection," and the death of only certain vulnerable subgroups of cells.

"An obvious follow-up is to look at other neurodegenerative diseases. Presumably, there would be a pattern of cellular deficits parallel to, but distinct from those of Huntington’s disease," said Cookson.

David Greenberg | EurekAlert!
Further information:
http://www.interscience.wiley.com

More articles from Life Sciences:

nachricht Researchers develop eco-friendly, 4-in-1 catalyst
25.04.2017 | Brown University

nachricht Transfecting cells gently – the LZH presents a GNOME prototype at the Labvolution 2017
25.04.2017 | Laser Zentrum Hannover e.V.

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

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...

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

NASA's Fermi catches gamma-ray flashes from tropical storms

25.04.2017 | Physics and Astronomy

Researchers invent process to make sustainable rubber, plastics

25.04.2017 | Materials Sciences

Transfecting cells gently – the LZH presents a GNOME prototype at the Labvolution 2017

25.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>