Featured Research

from universities, journals, and other organizations

Nerve Cells' Powerhouse "Clogged" In Lou Gehrig's Disease

Date:
July 19, 2004
Source:
Johns Hopkins Medical Institutions
Summary:
By studying rodent models of the relatively rare inherited form of Lou Gehrig's disease and tissue samples from a patient with the condition, scientists have discovered the first evidence that damage to nerve cell powerhouses is directly responsible for these cells' death.

By studying rodent models of the relatively rare inherited form of Lou Gehrig's disease and tissue samples from a patient with the condition, scientists have discovered the first evidence that damage to nerve cell powerhouses is directly responsible for these cells' death. The findings appear in the July 9 issue of Neuron.

Related Articles


The research team from the University of California San Diego, Johns Hopkins and elsewhere discovered that dysfunctional proteins clog the transport system that brings vital substances into mitochondria, the tiny organelles that provide energy to cells. This mitochondrial damage occurs in muscle-controlling nerve cells, the researchers report, helping explain the selective nature of inherited amyotrophic lateral sclerosis (ALS), or Lou Gehrig's disease.

"Mitochondria don't look normal in motor neurons in animal models of ALS and in patients with ALS, but this is the first study that links ALS and a specific problem with the mitochondria," says study co-author Jeffrey Rothstein, M.D., Ph.D., professor of neurology and director of the Robert Packard Center for ALS Research at Johns Hopkins.

The discovery provides new avenues to try to prevent or treat the progressive, fatal condition, say the researchers, and creates the possibility that mitochondria also might be involved in the more common forms of ALS or in other neurodegenerative diseases.

Inherited ALS, which accounts for less than 5 percent of ALS cases, is caused by a number of different mutations in the gene for superoxide dismutase, or SOD1, an enzyme that normally helps clean toxic molecules from cells. Each group of mice and rats studied by the researchers had been engineered to carry one of these mutations. By studying whole mitochondria purified from the brain, spinal cord and other tissues from the mice and rats, and a variety of samples taken from an ALS patient at autopsy, the researchers discovered that the outer mitochondrial surface was clogged with mutant SOD1 protein in spinal cord nerve cells but not in other tissues.

"In essence, the proteins literally gum up the works," says the study's leader, Don Cleveland, Ph.D., a scientist at UCSD and a researcher in the Packard Center.

The researchers suggest that the "works" for mitochondria in muscle-controlling nerves might be different from that in other cells. That uniqueness could explain why only the motor neurons' mitochondria are damaged and only those cells die, even though every cell in a rat, mouse or person with inherited ALS carries the instructions for the mutant SOD1. "We're viewing mitochondrial involvement as the greatest insult to the spinal cord cells in this form of ALS," Cleveland says. "We believe it's what pushes them over the edge."

The damaged mitochondria cause many problems and push the cell irreversibly toward death. "We've long known, for example, that having abnormal mitochondria makes neurons susceptible to injury from an excess of the chemical transmitter glutamate," says Rothstein, who notes that glutamate toxicity is a well-recognized aspect of ALS.

The scientists are beginning to test the potential role of mitochondrial involvement in the more common, sporadic forms of ALS and to try to target cell death and toxicity that stem from mitochondrial damage.

The study was funded by the U.S. National Institutes of Health, the Packard Center for ALS Research at Johns Hopkins, the Spinal Cord Foundation, the Bjorklund Foundation for ALS Research and the Paralyzed Veterans of America Spinal Cord Research Foundation.

Authors on this paper are Cleveland, Jian Liu, Concepcion Lillo, Christine Velde, Christopher Ward, Timothy Miller and David Williams of UCSD; Rothstein, Jamuna Subramaniam and Philip Wong of Johns Hopkins (Wong is also with the Packard Center); P. Andreas Jonsson, Peter Andersen, Stefan Marklund and Thomas Brannstrom at Umea University in Sweden; and Ole Gredal of the Bispebjerg Hospital in Copenhagen, Denmark.


Story Source:

The above story is based on materials provided by Johns Hopkins Medical Institutions. Note: Materials may be edited for content and length.


Cite This Page:

Johns Hopkins Medical Institutions. "Nerve Cells' Powerhouse "Clogged" In Lou Gehrig's Disease." ScienceDaily. ScienceDaily, 19 July 2004. <www.sciencedaily.com/releases/2004/07/040719090440.htm>.
Johns Hopkins Medical Institutions. (2004, July 19). Nerve Cells' Powerhouse "Clogged" In Lou Gehrig's Disease. ScienceDaily. Retrieved November 28, 2014 from www.sciencedaily.com/releases/2004/07/040719090440.htm
Johns Hopkins Medical Institutions. "Nerve Cells' Powerhouse "Clogged" In Lou Gehrig's Disease." ScienceDaily. www.sciencedaily.com/releases/2004/07/040719090440.htm (accessed November 28, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Friday, November 28, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Leaves Orphans Alone in Sierra Leone

Ebola Leaves Orphans Alone in Sierra Leone

AFP (Nov. 27, 2014) — The Ebola epidemic sweeping Sierra Leone is having a profound effect on the country's children, many of whom have been left without any family members to support them. Duration: 01:02 Video provided by AFP
Powered by NewsLook.com
Experimental Ebola Vaccine Shows Promise In Human Trial

Experimental Ebola Vaccine Shows Promise In Human Trial

Newsy (Nov. 27, 2014) — A recent test of a prototype Ebola vaccine generated an immune response to the disease in subjects. Video provided by Newsy
Powered by NewsLook.com
Pet Dogs to Be Used in Anti-Ageing Trial

Pet Dogs to Be Used in Anti-Ageing Trial

Reuters - Innovations Video Online (Nov. 26, 2014) — Researchers in the United States are preparing to discover whether a drug commonly used in human organ transplants can extend the lifespan and health quality of pet dogs. Video provided by Reuters
Powered by NewsLook.com
Today's Prostheses Are More Capable Than Ever

Today's Prostheses Are More Capable Than Ever

Newsy (Nov. 26, 2014) — Advances in prosthetics are making replacement body parts stronger and more lifelike than they’ve ever been. 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:

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