Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

LSUHSC research discovery provides therapeutic target for ALS

20.12.2012
Research led by Dr. Udai Pandey, Assistant Professor of Genetics at LSU Health Sciences Center New Orleans, has found that the ability of a protein made by a gene called FUS to bind to RNA is essential to the development of Amyotrophic Lateral Sclerosis (ALS).

This discovery identifies a possible therapeutic target for the fatal neurological disease. The research will be available online in the Advanced Access section of the journal Human Molecular Genetics website, posted by December 21, 2012. It will be published in an upcoming issue of the journal.

The current project advances Dr. Pandey's ALS research by teasing out specifically how the FUS gene causes the disease. To find out whether or not the RNA binding ability of FUS was required for the disease pathogenesis, the researchers mutated FUS RNA binding sites and produced a version of FUS that couldn't bind RNA, both with and without ALS mutations. They found that not only could they eliminate FUS RNA binding, but when they blocked RNA binding, they also suppressed ALS related neurodegeneration, demonstrating that the RNA binding ability of FUS is essential to the ALS disease process.

The researchers are working with fruit flies – the first animal model of FUS-related ALS, a model Dr. Pandey developed. The fruit flies were engineered to carry and express a mutated human FUS gene. This mutated FUS gene has been shown to be one of the causes of both familial and sporadic ALS. In the fruit flies, the resulting neurodegeneration impairs their ability to walk or climb and the defect is also easily visualized in the structure of their eyes. In addition, the flies carrying the defective FUS gene demonstrate hallmarks of the human disease, such as an age-dependent degeneration of neurons, accumulation of abnormal proteins and a decrease in life span. The fly model is a valuable resource for performing drug screens to identify drugs that could modify the effects of the mutated gene in humans.

"Our findings may pave the way for development of drugs targeting the biological processes responsible for causing ALS, and leading to treatments or prevention of this currently fatal, incurable condition, " notes Pandey. "The fly model is an inexpensive and fast way to study ALS as well as many human diseases such as cancer, Alzheimer's disease and Parkinson's disease. Many basic biological processes are well conserved between humans and fruit flies, and nearly 75% of human disease-causing genes are believed to have a functional partner (homolog) in the fly that makes these small animals a highly tractable model system."

"These intriguing findings inspire us and other researchers to search for drugs that can make the defective FUS protein less toxic by targeting is RNA binding as a potential therapeutic intervention," noted Gavin Daigle (Graduate student in the Pandey lab and leading author of the manuscript).

According to the National Institutes of Health, Amyotrophic Lateral Sclerosis, sometimes called Lou Gehrig's disease, is a rapidly progressive, invariably fatal neurological disease that attacks the nerve cells (neurons) responsible for controlling voluntary muscles. The disease belongs to a group of disorders known as motor neuron diseases, which are characterized by the gradual degeneration and death of motor neurons. Motor neurons are nerve cells located in the brain, brainstem, and spinal cord that serve as controlling units and vital communication links between the nervous system and the voluntary muscles of the body. Messages from motor neurons in the brain (called upper motor neurons) are transmitted to motor neurons in the spinal cord (called lower motor neurons) and from them to particular muscles. In ALS, both the upper motor neurons and the lower motor neurons degenerate or die, ceasing to send messages to muscles. Unable to function, the muscles gradually weaken, waste away (atrophy), and twitch (fasciculations). Eventually, the ability of the brain to start and control voluntary movement is lost.

The research team also included J Gavin Daigle, Dr. Nicholas A Lanson, Jr., Ian Casci, Dr. John Monaghan, Astha Maltare, and Dr. Charles Nichols at LSU Health Sciences Center New Orleans, Dr. Rebecca Smith from St. Jude Children's Research Center, and Dr. Frank Shewmaker and Dr. Dmitri Kryndushkin at the Uniformed Services University of the Health Sciences, Bethesda, MD.

The research was supported by funding from the Robert Packard Center for ALS at Johns Hopkins, the National Institutes of Health, and the Amyotrophic Lateral Sclerosis Association.

LSU Health Sciences Center New Orleans educates Louisiana's health care professionals. The state's academic health leader, LSUHSC New Orleans consists of a School of Medicine, the state's only School of Dentistry, Louisiana's only public School of Public Health, Schools of Allied Health Professions and Graduate Studies, and the only School of Nursing within an academic health center in the State of Louisiana. LSUHSC faculty take care of patients in public and private settings in the region, conduct research that improves the quality of life and generates jobs and economic impact, and perform service and outreach activities spanning the State. To learn more, visit http://www.lsuhsc.edu and http://www.twitter.com/LSUHSCHealth.

Leslie Capo | EurekAlert!
Further information:
http://www.lsuhsc.edu

More articles from Health and Medicine:

nachricht Organ-on-a-chip mimics heart's biomechanical properties
23.02.2017 | Vanderbilt University

nachricht Researchers identify cause of hereditary skeletal muscle disorder
22.02.2017 | Klinikum der Universität München

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Safe glide at total engine failure with ELA-inside

On January 15, 2009, Chesley B. Sullenberger was celebrated world-wide: after the two engines had failed due to bird strike, he and his flight crew succeeded after a glide flight with an Airbus A320 in ditching on the Hudson River. All 155 people on board were saved.

On January 15, 2009, Chesley B. Sullenberger was celebrated world-wide: after the two engines had failed due to bird strike, he and his flight crew succeeded...

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...

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

New pop-up strategy inspired by cuts, not folds

27.02.2017 | Materials Sciences

Sandia uses confined nanoparticles to improve hydrogen storage materials performance

27.02.2017 | Interdisciplinary Research

Decoding the genome's cryptic language

27.02.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>