Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Rare, lethal childhood disease tracked to protein

30.04.2013
A team of international researchers led by Northwestern Medicine scientists has identified how a defective protein plays a central role in a rare, lethal childhood disease known as Giant Axonal Neuropathy, or GAN. The finding is reported in the May 2013 Journal of Clinical Investigation.

GAN is an extremely rare and untreatable genetic disorder that strikes the central and peripheral nervous systems of young children. Those affected show no symptoms at birth; typically around age three the first signs of muscle weakness appear and progress slowly but steadily. Children with GAN experience increasing difficulty walking and are often wheelchair-bound by age 10. Over time, they become dependent on feeding and breathing tubes. Only a few will survive into young adulthood.

In GAN patients, nerve cells are swollen with massive build-ups of structures called intermediate filaments, cytoskeletal components that give cells their shape and mechanical properties. Goldman's team found that gigaxonin, a protein encoded by the gene involved in GAN, regulates normal turnover of the protein building blocks that form a cell's intermediate filaments. Mutations in this gene result in the malfunctioning of gigaxonin, which leads to the abnormal build-up of intermediate filaments and eventually disrupts the normal functioning of nerve cells.

"This important new research pinpoints the mechanism that allows intermediate filaments to rapidly build up in GAN patients," says Robert Goldman, chair of the department of cell and molecular biology at Northwestern University Feinberg School of Medicine. Goldman has studied the structural proteins of cells for more than 30 years.

"This is a huge step forward for GAN research," said Lori Sames, co-founder and CEO of Hannah's Hope Fund, the leading GAN disease organization. "GAN is juvenile ALS, but even worse. Not only do motor neurons die out, so do the sensory neurons. To find a medicinal therapy, you really need to know what mechanism to target. And thanks to Dr. Goldman's work, now we do."

To identify gigaxonin's role, scientists used cells known as fibroblasts obtained from skin biopsies of children with GAN. The cells were then grown in lab cultures, and they also contained large abnormal aggregates of intermediate filaments. When scientists introduced healthy gigaxonin genes into both control and patient fibroblasts, the results were dramatic. The abnormal aggregates of intermediate filaments disappeared. However, the cytoskeleton's two other major systems, microtubules and actin filaments were not affected by this treatment.

The study's lead author, Northwestern University postdoctoral fellow Saleemulla Mahammad, stressed that this discovery may also have implications for more common types of neurodegenerative diseases that are also characterized by large accumulations of intermediate filament proteins, including Alzheimer's disease and Parkinson's disease.

"Our results suggest new pathways for disease intervention," he said. "Finding a chemical component that can clear the intermediate filament aggregations and restore the normal distribution of intermediate filaments in cells could one day lead to a therapeutic agent for many neurological disorders."

Mahammad and other members of the Goldman Laboratory collaborated with Puneet Opal, M.D., associate professor in the Ken and Ruth Davee department of neurology and cell and molecular biology, along with researchers in the laboratory of Pascale Bomont, at the INSERM neurological institute in Montpelier, France, and the laboratory of Jean-Pierre Julien at the Université Laval in Quebec, Canada.

This research was supported by the National Institute of General Medical Sciences NIH grant 1P01GM096971-01 and Hannah's Hope Fund. The leading GAN disease foundation, Hannah's Hope Fund, was established in 2008, and currently knows of 38 cases of the disease worldwide. The foundation is currently working towards funding a clinical trial for GAN gene therapy.

Marla Paul | EurekAlert!
Further information:
http://www.northwestern.edu

More articles from Life Sciences:

nachricht Scientists discover species of dolphin that existed along South Carolina coast
24.08.2017 | New York Institute of Technology

nachricht The science of fluoride flipping
24.08.2017 | University of North Carolina Health Care

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

Scientists discover species of dolphin that existed along South Carolina coast

24.08.2017 | Life Sciences

The science of fluoride flipping

24.08.2017 | Life Sciences

Optimizing therapy planning for cancers of the liver

24.08.2017 | Medical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>