Featured Research

from universities, journals, and other organizations

Discovery provides therapeutic target for amyotrophic lateral sclerosis

Date:
December 19, 2012
Source:
Louisiana State University Health Sciences Center
Summary:
Researchers have 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.

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 Dec. 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.


Story Source:

The above story is based on materials provided by Louisiana State University Health Sciences Center. Note: Materials may be edited for content and length.


Journal Reference:

  1. J. Gavin Daigle, Nicholas A. Lanson, Jr, Rebecca B. Smith, Ian Casci, Astha Maltare, John Monaghan, Charles D. Nichols, Dmitri Kryndushkin, Frank Shewmaker, and Udai Bhan Pandey. RNA binding ability of FUS regulates neurodegeneration, cytoplasmic mislocalization and incorporation into stress granules associated with FUS carrying ALS-linked mutations. Human Molecular Genetics, 2012; DOI: 10.1093/hmg/dds526

Cite This Page:

Louisiana State University Health Sciences Center. "Discovery provides therapeutic target for amyotrophic lateral sclerosis." ScienceDaily. ScienceDaily, 19 December 2012. <www.sciencedaily.com/releases/2012/12/121219174322.htm>.
Louisiana State University Health Sciences Center. (2012, December 19). Discovery provides therapeutic target for amyotrophic lateral sclerosis. ScienceDaily. Retrieved October 20, 2014 from www.sciencedaily.com/releases/2012/12/121219174322.htm
Louisiana State University Health Sciences Center. "Discovery provides therapeutic target for amyotrophic lateral sclerosis." ScienceDaily. www.sciencedaily.com/releases/2012/12/121219174322.htm (accessed October 20, 2014).

Share This



More Health & Medicine News

Monday, October 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

How Nigeria Beat Its Ebola Outbreak

How Nigeria Beat Its Ebola Outbreak

Newsy (Oct. 20, 2014) The World Health Organization has declared Nigeria free of Ebola. Health experts credit a bit of luck and the government's initial response. Video provided by Newsy
Powered by NewsLook.com
Another Study Suggests Viagra Is Good For The Heart

Another Study Suggests Viagra Is Good For The Heart

Newsy (Oct. 20, 2014) An ingredient in erectile-dysfunction medications such as Viagra could improve heart function. Perhaps not surprising, given Viagra's history. Video provided by Newsy
Powered by NewsLook.com
Ebola Worries End for Dozens on U.S. Watch Lists

Ebola Worries End for Dozens on U.S. Watch Lists

Reuters - US Online Video (Oct. 20, 2014) Forty-three people who had contact with Thomas Eric Duncan, the first person diagnosed with Ebola in the U.S., were cleared overnight of twice-daily monitoring after 21 days of showing no symptoms. Rough Cut (no reporter narration). Video provided by Reuters
Powered by NewsLook.com
Fauci: Ebola Protocols to Focus on Training

Fauci: Ebola Protocols to Focus on Training

AP (Oct. 20, 2014) Dr. Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases, says he expects revised CDC protocols on Ebola to focus on training, observation and ensuring health care workers are more protected. (Oct. 20) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins