Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New hope for treatment of neurodegenerative disorder

22.04.2009
USC researchers uncover clues about cause of Huntington's disease

Researchers from the University of Southern California have taken an important first step toward protecting against Huntington disease using gene therapy.

Huntington Disease is an incurable neurological disorder characterized by uncontrolled movements, emotional instability and loss of intellectual faculties. It affects about 30,000 people in the United States, and children of parents with the disease have a 50 percent chance of inheriting it themselves.

"Our findings allow for the possibility that controlled over-expression of RCAN1-1L might in the future be a viable avenue for therapeutic intervention in Huntington disease patients," said Kelvin J. A. Davies, professor of gerontology in the USC Davis School of Gerontology and professor of biological sciences in the USC College of Letters, Arts and Sciences.

In a paper in the June 2009 issue of Journal of Biological Chemistry, now available online, Davies and his coauthors use cell culture findings to show that a form of the gene RCAN1, known as RCAN1-1L, is dramatically decreased in human brains affected by Huntington disease. RCAN1-1L was first discovered in Davies' lab.

The investigators also show that increasing levels of RCAN1-1L rescues cells from the toxic effects of Huntington disease, a result that could someday lead to new avenues of treatment, according to Davies.

"Our discovery offers real hope and may even have wide-ranging implications for a variety of other important CAG repeat-related diseases," Davies said.

While the Huntington gene, which makes the normal Huntington protein, is an essential component to healthy nerve cells, the mutant Huntington gene makes a toxic mutant Huntington protein. Mutant Huntington contains increased levels of the amino acid glutamine, which is generated by a repetition of the DNA triplet CAG.

A normal Huntington gene has a sequence of between six and 34 CAG repeats. Any strand of DNA possessing more than 40 CAG repeats indicates the carrier will develop Huntington disease, according to the researchers.

Indeed, the more repeats of CAG, the earlier the disease manifests itself and the more devastating the disease becomes. Currently available drugs do little more than help control erratic movements associated with the condition.

"It is important to keep in mind that these protective findings are in-vitro, meaning in cell cultures. Further proof of protection by RCAN1-1L will be required in-vivo, or in actual Huntington disease patients," said lead author Gennady Ermak, research associate professor at the USC Davis School of Gerontology.

Previous in-vitro research has revealed that adding the phosphate PO4, an inorganic chemical, to the mutant Huntington protein can protect against the mutant gene. This process is called phosphorylation, and can be achieved by either inhibiting an enzyme (calcineurin) or by activating an enzyme (Akt).

"Our findings point to increased phosphorylation of mutant Huntington through calcineurin inhibition as the likely mechanism by which RCAN1-1L may be protective against the mutant Huntington," Ermak said.

As Davies explained: "RCAN1-1L may actually play a role in the cause of Huntington disease."

"The gene is required to down-regulate the activity of calcineurin. We have previously linked too much RCAN1-1L expression to Alzheimer's disease," Davies said. "Thus, Alzheimer's disease and Huntington disease appear to involve opposite problems with RCAN1 expression and calcineurin activity."

In cases of Huntington disease, too little RCAN1-1L may allow calcineurin to act unopposed and remove too many phosphates from the mutant Huntington protein.

"We observed complete protection against the mutant Huntington by RCAN1-1L," Ermak said, but he reiterated the need for further research with Huntington disease patients.

The results offer a new direction for further research, Davies added.

Other aging disorders also associated with the expansion of repeated CAG code include: DRPLA (Dentratorubropallidoluysian atrophy), SBMA (Spinobulbar muscular atrophy or Kennedy disease) and SCA1 (Spinocerebellar ataxia Type 1).

Research was supported by the CHDI Foundation, Inc., and the High Q Foundation, both committed to the rapid discovery and development of drugs that delay or slow Huntington disease.

Suzanne Wu | EurekAlert!
Further information:
http://www.usc.edu

More articles from Life Sciences:

nachricht Antimicrobial substances identified in Komodo dragon blood
23.02.2017 | American Chemical Society

nachricht New Mechanisms of Gene Inactivation may prevent Aging and Cancer
23.02.2017 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)

All articles from Life Sciences >>>

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

From rocks in Colorado, evidence of a 'chaotic solar system'

23.02.2017 | Physics and Astronomy

'Quartz' crystals at the Earth's core power its magnetic field

23.02.2017 | Earth Sciences

Antimicrobial substances identified in Komodo dragon blood

23.02.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>