Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Nerve Cells’ Powerhouse "Clogged" in Lou Gehrig’s Disease

15.07.2004


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.



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.

| newswise
Further information:
http://www.hopkinsmedicine.org
http://www.alscenter.org

More articles from Life Sciences:

nachricht Molecular Force Sensors
20.09.2017 | Max-Planck-Institut für Biochemie

nachricht Foster tadpoles trigger parental instinct in poison frogs
20.09.2017 | Veterinärmedizinische Universität Wien

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

Im Focus: Fast, convenient & standardized: New lab innovation for automated tissue engineering & drug

MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems Holding GmbH about commercial use of a multi-well tissue plate for automated and reliable tissue engineering & drug testing.

MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems...

Im Focus: Silencing bacteria

HZI researchers pave the way for new agents that render hospital pathogens mute

Pathogenic bacteria are becoming resistant to common antibiotics to an ever increasing degree. One of the most difficult germs is Pseudomonas aeruginosa, a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Molecular Force Sensors

20.09.2017 | Life Sciences

Producing electricity during flight

20.09.2017 | Power and Electrical Engineering

Tiny lasers from a gallery of whispers

20.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>