Featured Research

from universities, journals, and other organizations

Lipid Abnormalities Linked To Lou Gehrig’s Disease

Date:
August 22, 2002
Source:
NIH/National Institute On Aging
Summary:
Abnormal accumulation of two common lipids in motor nerve cells could play a critical role in the development of amyotrophic lateral sclerosis (ALS), according to investigators at the National Institute on Aging (NIA) in Baltimore. The finding could help scientists develop drugs and other treatments that might one day slow or arrest the disease's progression.

Abnormal accumulation of two common lipids in motor nerve cells could play a critical role in the development of amyotrophic lateral sclerosis (ALS), according to investigators at the National Institute on Aging (NIA) in Baltimore. The finding could help scientists develop drugs and other treatments that might one day slow or arrest the disease's progression.

Related Articles


"ALS is a terrible disease in which a fully functioning mind is trapped inside a body that is becoming progressively paralyzed. At the present time, nothing can be done for ALS, but we hope this newly established link between lipid regulation and the disease will hasten the development of new treatments," said Mark Mattson, Ph.D., lead author of the study and chief of the NIA Laboratory of Neurosciences. Lipids are the building blocks of fats. The study is available online at the Annals of Neurology website, http://www.interscience.wiley.com/annalsofneurology and will be published in the journal's September 2002 issue.

Also called Lou Gehrig's disease, ALS is a progressive, fatal neurological disease affecting as many as 20,000 Americans, with 5,000 new cases occurring in the United States each year. Patients usually die within five years of diagnosis. ALS occurs when specific nerve cells in the brain and spinal cord that control voluntary movement gradually degenerate. The loss of these motor neurons causes the muscles under their control to weaken and waste away, leading to paralysis. In some instances, the disease is inherited, but in most cases the cause is unknown.

But NIA scientists unearthed several new clues through a complex, multi-step investigation. After comparing spinal cord tissue extracted from people who had ALS with those who didn't, the investigators discovered that levels of ceramides, cholesterol esters and several other lipids were significantly elevated in the spinal cords of people with ALS.

To test whether these elevated levels of ceramides, a cell wall component, and cholesterol esters, a form of cholesterol, cause motor neuron degeneration associated with ALS, the investigators studied mice with a mutated human gene, called copper/zinc-superoxide dismutase (Cu/Zn-SOD), incorporated into their genome. The mice with this mutated gene, which causes some forms of inherited ALS in humans, developed progressive motor neuron degeneration in their spinal cords, became paralyzed and eventually died. As in humans, analysis of the spinal cords of these animals revealed increased levels of ceramides and cholesterol esters.

To determine what might cause these abnormalities in lipid metabolism, the investigators exposed mouse motor neurons to free radicals--molecules with unpaired electrons that can damage cells and tissues--because previous studies suggested that increased production of oxygen free radicals is involved in the onset and progression of ALS. As a result, ceramides and cholesterol esters are increased in the exposed cells, just as was found in motor neurons affected by ALS.

Building on this finding, Dr. Mattson and his colleagues conducted experiments to determine if accumulation of ceramides and cholesterol esters in these neurons could be blocked when treated with a drug called ISP-1. The drug prevents the formation of large membrane molecules called sphingolipids, which, in turn, produce ceramides. When exposed to oxygen free radicals, motor neurons treated with ISP-1 did not accumulate ceramides and cholesterol esters, nor did they degenerate. However, untreated motor neurons that were exposed directly to ceramides did deteriorate.

"Based on our study, ceramide accumulation appears to be both necessary and sufficient to explain the degeneration of spinal cord motor neurons in ALS," Dr. Mattson says. "This knowledge is now being used to develop drugs that potentially could prevent these abnormalities."

In addition to drugs, the NIA scientists are investigating whether changes in dietary intake of cholesterol and lipids involved in the formation of membrane sphingolipids might have an impact on an individual's susceptibility to ALS.

The NIA leads the Federal effort supporting and conducting biomedical, clinical, social, and behavioral research on aging. This effort includes research into the causes and treatment of Alzheimer's disease, Parkinson's disease, and other neurodegenerative disorders associated with age. Press releases, fact sheets, and other materials about aging and aging research can be viewed at the NIA's general information Web site, http://www.nia.nih.gov.

Reference: Cutler RG, Pedersen WA, Camandola, S, Rothstein, JD, and Mattson, MP, "Evidence That Accumulation of Ceramides and Cholesterol Esters Mediates Oxidative Stress--Induced Death of Motor Neurons in Amyotrophic Lateral Sclerosis," Annals of NeurologyΈ vol. 52 (2002).


Story Source:

The above story is based on materials provided by NIH/National Institute On Aging. Note: Materials may be edited for content and length.


Cite This Page:

NIH/National Institute On Aging. "Lipid Abnormalities Linked To Lou Gehrig’s Disease." ScienceDaily. ScienceDaily, 22 August 2002. <www.sciencedaily.com/releases/2002/08/020822070004.htm>.
NIH/National Institute On Aging. (2002, August 22). Lipid Abnormalities Linked To Lou Gehrig’s Disease. ScienceDaily. Retrieved April 21, 2015 from www.sciencedaily.com/releases/2002/08/020822070004.htm
NIH/National Institute On Aging. "Lipid Abnormalities Linked To Lou Gehrig’s Disease." ScienceDaily. www.sciencedaily.com/releases/2002/08/020822070004.htm (accessed April 21, 2015).

Share This


More From ScienceDaily



More Health & Medicine News

Tuesday, April 21, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Blue Bell Recalls All Products

Blue Bell Recalls All Products

AP (Apr. 21, 2015) — Blue Bell Creameries voluntary recalled for all of its products after two samples of chocolate chip cookie dough ice cream tested positive for listeria, a potentially deadly bacteria. Blue Bell&apos;s President and CEO issued a video statement. (April 21) Video provided by AP
Powered by NewsLook.com
'Tutu Tuesdays' Brighten Faces at Kids' Hospital

'Tutu Tuesdays' Brighten Faces at Kids' Hospital

AP (Apr. 21, 2015) — Doctors and nurses have started wearing ballet tutus every Tuesday to cheer up young hospital patients at a Florida hospital. It started with a request made by a nervous patient -- now, almost the entire staff is wearing the tutus. (April 21) Video provided by AP
Powered by NewsLook.com
Humanoid Robot Can Recognise and Interact With People

Humanoid Robot Can Recognise and Interact With People

Reuters - Innovations Video Online (Apr. 20, 2015) — An ultra-realistic humanoid robot called &apos;Han&apos; recognises and interprets people&apos;s facial expressions and can even hold simple conversations. Developers Hanson Robotics hope androids like Han could have uses in hospitality and health care industries where face-to-face communication is vital. Matthew Stock reports. Video provided by Reuters
Powered by NewsLook.com
Labour Party Warns Britain's Health Service 'on Life Support'

Labour Party Warns Britain's Health Service 'on Life Support'

AFP (Apr. 20, 2015) — Britain&apos;s opposition Labour Party Monday claimed the National Health Service (NHS) was &apos;on life support&apos; as it turned its attention to the state-run service, which is a key issue for the UK&apos;s May 7 general election. 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:

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