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 Small but ver­sat­ile; key play­ers in the mar­ine ni­tro­gen cycle can util­ize cy­anate and urea
10.12.2018 | Max-Planck-Institut für Marine Mikrobiologie

nachricht Carnegie Mellon researchers probe hydrogen bonds using new technique
10.12.2018 | Carnegie Mellon University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Researchers develop method to transfer entire 2D circuits to any smooth surface

What if a sensor sensing a thing could be part of the thing itself? Rice University engineers believe they have a two-dimensional solution to do just that.

Rice engineers led by materials scientists Pulickel Ajayan and Jun Lou have developed a method to make atom-flat sensors that seamlessly integrate with devices...

Im Focus: Three components on one chip

Scientists at the University of Stuttgart and the Karlsruhe Institute of Technology (KIT) succeed in important further development on the way to quantum Computers.

Quantum computers one day should be able to solve certain computing problems much faster than a classical computer. One of the most promising approaches is...

Im Focus: Substitute for rare earth metal oxides

New Project SNAPSTER: Novel luminescent materials by encapsulating phosphorescent metal clusters with organic liquid crystals

Nowadays energy conversion in lighting and optoelectronic devices requires the use of rare earth oxides.

Im Focus: A bit of a stretch... material that thickens as it's pulled

Scientists have discovered the first synthetic material that becomes thicker - at the molecular level - as it is stretched.

Researchers led by Dr Devesh Mistry from the University of Leeds discovered a new non-porous material that has unique and inherent "auxetic" stretching...

Im Focus: The force of the vacuum

Scientists from the Theory Department of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science (CFEL) in Hamburg have shown through theoretical calculations and computer simulations that the force between electrons and lattice distortions in an atomically thin two-dimensional superconductor can be controlled with virtual photons. This could aid the development of new superconductors for energy-saving devices and many other technical applications.

The vacuum is not empty. It may sound like magic to laypeople but it has occupied physicists since the birth of quantum mechanics.

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

New Plastics Economy Investor Forum - Meeting Point for Innovations

10.12.2018 | Event News

EGU 2019 meeting: Media registration now open

06.12.2018 | Event News

Expert Panel on the Future of HPC in Engineering

03.12.2018 | Event News

 
Latest News

Small but ver­sat­ile; key play­ers in the mar­ine ni­tro­gen cycle can util­ize cy­anate and urea

10.12.2018 | Life Sciences

New method gives microscope a boost in resolution

10.12.2018 | Physics and Astronomy

Carnegie Mellon researchers probe hydrogen bonds using new technique

10.12.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>