Featured Research

from universities, journals, and other organizations

Common RNA pathway found in ALS and dementia

Date:
September 30, 2012
Source:
University of California - San Diego
Summary:
Two proteins previously found to contribute to ALS, also known as Lou Gehrig's disease, have divergent roles. But a new study shows that a common pathway links them.

Two proteins previously found to contribute to ALS, also known as Lou Gehrig's disease, have divergent roles. But a new study, led by researchers at the Department of Cellular and Molecular Medicine at the University of California, San Diego School of Medicine, shows that a common pathway links them.

The discovery reveals a small set of target genes that could be used to measure the health of motor neurons, and provides a useful tool for development of new pharmaceuticals to treat the devastating disorder, which currently has no treatment or cure.

Funded in part by the National Institutes of Health and the California Institute for Regenerative Medicine (CIRM), the study will be published in the advance online edition of Nature Neuroscience on September 30.

ALS is an adult-onset neurodegenerative disorder characterized by premature degeneration of motor neurons, resulting in a progressive, fatal paralysis in patients.

The two proteins that contribute to the disease -- FUS/TLS and TDP-43 -- bind to ribonucleic acid (RNA), intermediate molecules that translate genetic information from DNA to proteins. In normal cells, both TDP-43 and FUS/TLS are found in the nucleus where they help maintain proper levels of RNA. In the majority of ALS patients, however, these proteins instead accumulate in the cell's cytoplasm -- the liquid that separates the nucleus from the outer membrane, and thus are excluded from the nucleus, which prevents them from performing their normal duties.

Since the proteins are in the wrong location in the cell, they are unable to perform their normal function, according to the study's lead authors, Kasey R. Hutt, Clotilde Lagier-Tourenne and Magdalini Polymenidou. "In diseased motor neurons where TDP-43 is cleared from the nucleus and forms cytoplasmic aggregates," the authors wrote, "we saw lower protein levels of three genes regulated by TDP-43 and FUS/TLS. We predicted that this, based on our mouse studies, and found the same results in neurons derived from human embryonic stem cells."

In 2011, this team of UC San Diego scientists discovered that more than one-third of the genes in the brains of mice are direct targets of TDP-43, affecting the functions of these genes. In the new study, they compared the impact of the FUS/TLS protein to that of TDP-43, hoping to find a large target overlap.

"Surprisingly, instead we saw a relatively small overlap, and the common RNA targets genes contained exceptionally long introns, or non-coding segments. The set is composed of genes that are important for synapse function," said principal investigator Gene Yeo, PhD, assistant professor in the Department of Cellular and Molecular Medicine and the Institute for Genomic Medicine at UC San Diego and a visiting professor at the Molecular Engineering Laboratory in Singapore. "Loss of this common overlapping set of genes is evidence of a common pathway that appears to contribute to motor neuron degeneration."

In an effort to understand the normal function of these two RNA binding proteins, the scientists knocked down the proteins in brains of mice to mimic nuclear clearance, using antisense oligonucleotide technology developed in collaboration with ISIS Pharmaceuticals. The study resulted in a list of genes that are up or down regulated, and the researchers duplicated the findings in human cells.

"If we can somehow rescue the genes from down regulation, or being decreased by these proteins, it could point to a drug target for ALS to slow or halt degeneration of the motor neurons," said Yeo.

These proteins also look to be a central component in other neurodegenerative conditions. For example, accumulating abnormal TDP-43 and FUS/TLS in neuronal cytoplasm has been documented in frontotemporal lobar dementia, a neurological disorder that has been shown to be genetically and clinically linked to ALS, and which is the second most frequent cause of dementia after Alzheimer's disease.


Story Source:

The above story is based on materials provided by University of California - San Diego. Note: Materials may be edited for content and length.


Journal Reference:

  1. Clotilde Lagier-Tourenne, Magdalini Polymenidou, Kasey R Hutt, Anthony Q Vu, Michael Baughn, Stephanie C Huelga, Kevin M Clutario, Shuo-Chien Ling, Tiffany Y Liang, Curt Mazur, Edward Wancewicz, Aneeza S Kim, Andy Watt, Sue Freier, Geoffrey G Hicks, John Paul Donohue, Lily Shiue, C Frank Bennett, John Ravits, Don W Cleveland, Gene W Yeo. Divergent roles of ALS-linked proteins FUS/TLS and TDP-43 intersect in processing long pre-mRNAs. Nature Neuroscience, 2012; DOI: 10.1038/nn.3230

Cite This Page:

University of California - San Diego. "Common RNA pathway found in ALS and dementia." ScienceDaily. ScienceDaily, 30 September 2012. <www.sciencedaily.com/releases/2012/09/120930142108.htm>.
University of California - San Diego. (2012, September 30). Common RNA pathway found in ALS and dementia. ScienceDaily. Retrieved September 2, 2014 from www.sciencedaily.com/releases/2012/09/120930142108.htm
University of California - San Diego. "Common RNA pathway found in ALS and dementia." ScienceDaily. www.sciencedaily.com/releases/2012/09/120930142108.htm (accessed September 2, 2014).

Share This




More Health & Medicine News

Tuesday, September 2, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Get on Your Bike! London Cycling Popularity Soars Despite Danger

Get on Your Bike! London Cycling Popularity Soars Despite Danger

AFP (Sep. 1, 2014) Wedged between buses, lorries and cars, cycling in London isn't for the faint hearted. Nevertheless the number of people choosing to bike in the British capital has doubled over the past 15 years. Duration: 02:27 Video provided by AFP
Powered by NewsLook.com
Can You Train Your Brain To Eat Healthy?

Can You Train Your Brain To Eat Healthy?

Newsy (Sep. 1, 2014) New research says if you condition yourself to eat healthy foods, eventually you'll crave them instead of junk food. Video provided by Newsy
Powered by NewsLook.com
We've Got Mites Living In Our Faces And So Do You

We've Got Mites Living In Our Faces And So Do You

Newsy (Aug. 30, 2014) A new study suggests 100 percent of adult humans (those over 18 years of age) have Demodex mites living in their faces. Video provided by Newsy
Powered by NewsLook.com
Liberia Continues Fight Against Ebola

Liberia Continues Fight Against Ebola

AFP (Aug. 30, 2014) Authorities in Liberia try to stem the spread of the Ebola epidemic by raising awareness and setting up sanitation units for people to wash their hands. Duration: 00:41 Video provided by AFP
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:
from the past week

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