Featured Research

from universities, journals, and other organizations

New Down Syndrome Gene Identified By Stanford/Packard Scientists

Date:
July 6, 2006
Source:
Stanford University Medical Center
Summary:
Researchers at the Stanford University School of Medicine and Lucile Packard Children's Hospital have identified one possible cause of mental retardation in Down syndrome.

Researchers at the Stanford University School of Medicine and Lucile Packard Children’s Hospital have identified one possible cause of mental retardation in Down syndrome. The culprit is a gene that, when overexpressed, causes neurons responsible for attention and memory to shrivel and stop functioning normally. The finding offers the first glimmer of hope that doctors could one day interfere with or even reverse the cognitive decline that frequently affects those with Down syndrome in middle age.

“We may now have the opportunity to make a big difference in people’s lives,” said neurologist William Mobley, MD, PhD. “If we can decrease the expression of this gene we may be able to provide something more than supportive care to people with Down syndrome.”

Mobley, who is the John E. Cahill Family Professor at Stanford’s School of Medicine and director of Lucile Packard Children’s Hospital’s Down Syndrome Center, is the senior author of the research, published in the July 6 issue of Neuron. He is also the director of Stanford’s Neuroscience Institute.

More than 300,000 people nationwide have Down syndrome, which is caused by an extra copy of chromosome 21, giving them a total of three. Although it is the leading cause of mental retardation in the country, little research has been conducted at the molecular or neurological level to understand and explore potential therapies for its symptoms. In addition to dealing with early cognitive difficulties, childhood heart disease and leukemia, most people with Down syndrome develop Alzheimer’s disease by the age of 40.

“Down syndrome results in an extraordinarily complex constellation of symptoms,” said lead author and senior research scientist Ahmad Salehi, MD, PhD. “We’ve done what many people thought was impossible: We’ve dissected it genetically to correlate one of the most troubling symptoms—cognitive dysfunction—with one particular gene. While it’s not the only gene involved, its presence in three copies makes a significant difference.”

Although mutations in the gene, called App for amyloid precursor protein, can cause early-onset Alzheimer’s disease in otherwise healthy people, this is the first time it has been linked directly to degeneration of a specific group of neurons in the brains of those with Down syndrome. The breakthrough confirms an idea suggested by previous research: Neuronal degradation in people with Down syndrome is the result of an interrupted conversation between nerve cells in a specific part of the brain.

Like a classroom troublemaker, a signaling neuron needs feedback to thrive. It lobs specialized compounds called neurotransmitters toward its neighbor and awaits a response to its molecular spit wads. The target cell fires back such molecules as nerve growth factor, or NGF. The NGF is engulfed by the membrane of the instigator cell and is shuttled to the cell body in a process called retrograde transport. Once there it acts on the nucleus to stimulate the expression of genes that support neuronal growth. Interrupting this intercellular tit-for-tat causes the neuron to wither away.

Salehi, Mobley and their colleagues used a mouse model of Down syndrome to follow NGF’s journey from the membrane to the cell body of the signaling cell. They focused on a mouse in which only about 140 genes—including App—were present in three copies. They found that although NGF retrograde transport was severely compromised in this mouse, it was markedly increased when the third copy of App was deleted. The neurons in the brain of the mouse with two copies of App were also larger than those in the mouse with three copies. “Clearly, App influences the transport of NGF in Down syndrome,” said Mobley, “and we’re very suspicious that it may do something similar in Alzheimer’s disease. We’re now investigating ways in which we might be able to turn down App expression.”

Added Salehi, “It’s not even necessary to turn it off completely. All we need to do is to reduce it by one-third: From 150 percent of normal back down to 100 percent.”

Although it’s not clear exactly how App interferes with NGF transport, a clue can be found in the intracellular compartments called endosomes that shuttle NGF to the nucleus. Mouse cells with three copies of App have endosomes that are abnormally large, perhaps making them too unwieldy to transport NGF. A similar ballooning of neuronal endosomes has been noted in people with Down syndrome and Alzheimer’s disease.

The findings are tantalizing, yet many steps remain to an effective therapy for these devastating disorders, the researchers cautioned. The fact that deleting the third copy of App didn’t restore the mouse to normal indicates that other genes must also affect the timing or severity of the neuronal degeneration. But Mobley and Salehi have already embarked on an ambitious plan.

“First we need to figure out at a molecular level how App works in Down syndrome,” said Mobley. “Then we need to examine other genes that might be involved and test possible compounds in mouse and human cells. If we are able to do all that, we might begin to think of helping children and adults with Down syndrome to develop and age more normally.”


Story Source:

The above story is based on materials provided by Stanford University Medical Center. Note: Materials may be edited for content and length.


Cite This Page:

Stanford University Medical Center. "New Down Syndrome Gene Identified By Stanford/Packard Scientists." ScienceDaily. ScienceDaily, 6 July 2006. <www.sciencedaily.com/releases/2006/07/060706100625.htm>.
Stanford University Medical Center. (2006, July 6). New Down Syndrome Gene Identified By Stanford/Packard Scientists. ScienceDaily. Retrieved July 28, 2014 from www.sciencedaily.com/releases/2006/07/060706100625.htm
Stanford University Medical Center. "New Down Syndrome Gene Identified By Stanford/Packard Scientists." ScienceDaily. www.sciencedaily.com/releases/2006/07/060706100625.htm (accessed July 28, 2014).

Share This




More Health & Medicine News

Monday, July 28, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Traditional African Dishes Teach Healthy Eating

Traditional African Dishes Teach Healthy Eating

AP (July 28, 2014) Classes are being offered nationwide to encourage African Americans to learn about cooking fresh foods based on traditional African cuisine. The program is trying to combat obesity, heart disease and other ailments often linked to diet. (July 28) Video provided by AP
Powered by NewsLook.com
West Africa Gripped by Deadly Ebola Outbreak

West Africa Gripped by Deadly Ebola Outbreak

AFP (July 28, 2014) The worst-ever outbreak of the deadly Ebola epidemic grips west Africa, killing hundreds. Duration: 00:48 Video provided by AFP
Powered by NewsLook.com
Trees Could Save More Than 850 Lives Each Year

Trees Could Save More Than 850 Lives Each Year

Newsy (July 27, 2014) A national study conducted by the USDA Forest Service found that trees collectively save more than 850 lives on an annual basis. Video provided by Newsy
Powered by NewsLook.com
Google's Next Frontier: The Human Body

Google's Next Frontier: The Human Body

Newsy (July 27, 2014) Google is collecting genetic and molecular information to paint a picture of the perfectly healthy human. 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