Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Molecular trigger for Huntington’s disease found

07.07.2005


Researchers have discovered a key regulatory molecule whose overactivation by the abnormal protein produced in Huntington’s disease (HD) causes the central pathologies of the disease. The abnormal HD protein activates the regulatory protein called p53, which in turn switches on a host of other genes. This abnormal gene activation damages the cells’ power plants, called the mitochondria, and kills brain cells.



The researchers also speculated that disturbances in p53 may also play a role in some forms of Parkinson’s disease and amyotrophic lateral sclerosis, or Lou Gehrig’s disease.

Ironically, p53 is the same regulatory protein that is inactivated in a large fraction of cancers. This inactivation allows abnormal cancer cells to escape the cell’s protective "suicide program" that would normally kill them. The researchers theorize that the lower incidence of cancer in HD patients could be caused by the protective effect of overactive p53.


In the July 7, 2005, issue of Neuron, Akira Sawa and colleagues at Johns Hopkins University School of Medicine reported experiments ranging from molecular studies in cultured brain cells to analysis of the brains of human HD patients that demonstrated the central role of p53 in the pathologies of HD.

Their studies with cell cultures showed that the abnormal HD protein selectively binds to p53 and increases its level in cells. They noted that the brains of patients with HD also show substantial increases in the p53 protein, with the highest levels in cases with the most extensive pathology.

The researchers’ experiments also revealed that this p53 increase causes an overactivation in the genes regulated by p53, which is called a "nuclear transcription factor" because it regulates the transcription of its target genes in cell nuclei.

In studies of cell cultures and of mice engineered to have HD, the researchers found that the p53 increase causes malfunctions in mitochondria. What’s more, they found that this p53 increase induced by the abnormal HD protein greatly increases cell death.

The researchers also found effects of the abnormality in p53 in whole animals. They found that deleting p53 suppresses damage to neurons in the eye of fruit flies engineered to have the abnormal HD protein. And in mice with the abnormal protein, knocking out p53 corrects behavioral abnormalities that the mice otherwise display. These behaviors include abnormal reflexes such as an inhibited startle response to loud noise, which is also present in human HD patients.

"In summary, our study establishes a specific role for p53 in HD," concluded Sawa and colleagues. "As p53 is a nuclear transcription factor that regulates various mitochondrial genes and insofar as mitochondrial dysfunction appears important in HD, our findings provide a molecular mechanism linking disturbances of nuclei and mitochondria in HD." Download PDF

Heidi Hardman | EurekAlert!
Further information:
http://www.cell.com

More articles from Life Sciences:

nachricht Making fuel out of thick air
08.12.2017 | DOE/Argonne National Laboratory

nachricht ‘Spying’ on the hidden geometry of complex networks through machine intelligence
08.12.2017 | Technische Universität Dresden

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Scientists channel graphene to understand filtration and ion transport into cells

Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.

To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...

Im Focus: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

Im Focus: Successful Mechanical Testing of Nanowires

With innovative experiments, researchers at the Helmholtz-Zentrums Geesthacht and the Technical University Hamburg unravel why tiny metallic structures are extremely strong

Light-weight and simultaneously strong – porous metallic nanomaterials promise interesting applications as, for instance, for future aeroplanes with enhanced...

Im Focus: Virtual Reality for Bacteria

An interdisciplinary group of researchers interfaced individual bacteria with a computer to build a hybrid bio-digital circuit - Study published in Nature Communications

Scientists at the Institute of Science and Technology Austria (IST Austria) have managed to control the behavior of individual bacteria by connecting them to a...

Im Focus: A space-time sensor for light-matter interactions

Physicists in the Laboratory for Attosecond Physics (run jointly by LMU Munich and the Max Planck Institute for Quantum Optics) have developed an attosecond electron microscope that allows them to visualize the dispersion of light in time and space, and observe the motions of electrons in atoms.

The most basic of all physical interactions in nature is that between light and matter. This interaction takes place in attosecond times (i.e. billionths of a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

 
Latest News

Midwife and signpost for photons

11.12.2017 | Physics and Astronomy

How do megacities impact coastal seas? Searching for evidence in Chinese marginal seas

11.12.2017 | Earth Sciences

PhoxTroT: Optical Interconnect Technologies Revolutionized Data Centers and HPC Systems

11.12.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>