Featured Research

from universities, journals, and other organizations

Unravelling nerve-cell death in rare children's disease

Date:
March 25, 2014
Source:
Sanford-Burnham Medical Research Institute
Summary:
Mutations in a protein that plays a role in the body’s DNA repair system has been discovered by researchers, similar to what’s observed in the rare children’s disease ataxia-telangiectasia. The discovery provides an approach to identifying therapies that will resuscitate the broken DNA repair mechanism.

A team of scientists, led by Stuart Lipton, M.D., Ph.D., professor and director of the Neuroscience and Aging Research Center at Sanford-Burnham Medical Research Institute (Sanford-Burnham), recently discovered why cerebellar granule cell neurons in patients suffering from ataxia-telangiectasia (A-T) were unable to repair DNA damage and thus died.

A-T is a hereditary condition that begins early in childhood, and causes a gradual loss of certain nerve cells in the cerebellum of the brain. A-T occurs in about 1 in 40,000 births, with symptoms including severe loss of muscle control, dilated small blood vessels, repeated infections in the sinus and lungs, and it frequently leads to cancers such as lymphoma or leukemia. Today, thanks to improved treatment of infections and cancer, many patients live into their 30s or longer.

His study, with Nobuki Nakanishi, Ph.D., associate professor in Sanford-Burnham's Degenerative Disease Program, was published March 25 in The Journal of Neuroscience. The researchers used genetically engineered mice to show that myoctye-enhancer factor 2D (MEF2D), a transcription factor that turns on specific genes involved in cell survival, is activated after binding to a protein known as A-T mutated (ATM). When the ATM gene that codes for the ATM protein is mutated, thus causing A-T, ATM-MEF2D-survival signals in response to DNA damage are ineffective and may contribute to neurodegeneration.

"This is the first time that a signal that regulates MEF2D-dependent survival in response to DNA damage has been identified," said Lipton. "Knowing that ATM-mediated activation of MEF2D promotes survival in cerebellar neurons in response to DNA damage may provide a therapeutic opportunity for A-T. For example, if we can confirm that defects in the ATM-MEF2D signal contribute to A-T, we can search for molecules that enhance MEF2D activity to 'revive' the DNA repair system."

"As parents, we are excited that this research could lead to new ideas about how to slow the brain cell loss seen in our kids, improving their ability to walk, talk, and eat. This could lead to big improvements in their quality of life," said Brad Margus, voluntary president and founder of the A-T Children's Project.

In general, DNA repair systems are essential for cellular integrity and stability. DNA can be damaged in many ways, including UV rays, tobacco, and oxidative damage from byproducts of metabolism, such as free radicals. Inherited defects of DNA repair systems can lead to many types of cancer, dwarfism, growth and mental retardation, deafness -- as well as A-T.

"Prior to this study, we knew that p53 -- a protein known as the guardian angel of the genome -- was a target of ATM activation and contributes to the control and efficacy of DNA repair. Now, we have shown another pathway whereby MEF2D participates in DNA damage repair in the cerebellum. The fact that there is an abundance of MEF2D in the cerebellum, and that ATM mutations are associated with A-T, adds support to the proposed ATM-MEF2D dysfunction as a cause of A-T," said Lipton.

"Moving forward, we will be interested to see if this mechanism contributes to other rare hereditary diseases with defects in DNA repair."


Story Source:

The above story is based on materials provided by Sanford-Burnham Medical Research Institute. Note: Materials may be edited for content and length.


Journal Reference:

  1. S. F. Chan, S. Sances, L. M. Brill, S.-i. Okamoto, R. Zaidi, S. R. McKercher, M. W. Akhtar, N. Nakanishi, S. A. Lipton. ATM-Dependent Phosphorylation of MEF2D Promotes Neuronal Survival after DNA Damage. Journal of Neuroscience, 2014; 34 (13): 4640 DOI: 10.1523/JNEUROSCI.2510-12.2014

Cite This Page:

Sanford-Burnham Medical Research Institute. "Unravelling nerve-cell death in rare children's disease." ScienceDaily. ScienceDaily, 25 March 2014. <www.sciencedaily.com/releases/2014/03/140325190712.htm>.
Sanford-Burnham Medical Research Institute. (2014, March 25). Unravelling nerve-cell death in rare children's disease. ScienceDaily. Retrieved September 2, 2014 from www.sciencedaily.com/releases/2014/03/140325190712.htm
Sanford-Burnham Medical Research Institute. "Unravelling nerve-cell death in rare children's disease." ScienceDaily. www.sciencedaily.com/releases/2014/03/140325190712.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

U.N. Says Ebola Travel Restrictions Will Cause Food Shortage

U.N. Says Ebola Travel Restrictions Will Cause Food Shortage

Newsy (Sep. 2, 2014) The U.N. says the problem is two-fold — quarantine zones and travel restrictions are limiting the movement of both people and food. Video provided by Newsy
Powered by NewsLook.com
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

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