Featured Research

from universities, journals, and other organizations

Neuron-damaging mechanism discovered in mouse model of inherited ALS

Date:
August 27, 2010
Source:
Cell Press
Summary:
New research uncovers what may be a primary neuron-damaging insult that occurs in an inherited form of a devastating neurodegenerative disorder. The study describes a critical mechanistic link between a mutant protein and disease pathogenesis in an animal model of amyotrophic lateral sclerosis (ALS).

New research uncovers what may be a primary neuron-damaging insult that occurs in an inherited form of a devastating neurodegenerative disorder. The study, published in the August 26th issue of the journal Neuron, describes a critical mechanistic link between a mutant protein and disease pathogenesis in an animal model of amyotrophic lateral sclerosis (ALS).

Related Articles


ALS is a disease that attacks the neurons in the brain and spinal cord that control voluntary movement. There is no cure for ALS, which typically develops in adults and is characterized by a progressive paralysis that often leads to death within three to five years of diagnosis. About 10% of ALS cases are inherited and a portion of those are attributed to mutations in the gene for a protein called SOD1. However, the exact mechanism that links mutant SOD1 with motor neuron degeneration has not been established.

Malfunction of mitochondria, tiny intracellular energy-producing structures, has also been implicated in ALS pathology. "Previous research using rodent models and human samples showed that mutant SOD1 is associated with the outer surface of mitochondria in affected but not unaffected tissues," explains senior study author, Professor Don W. Cleveland from the University of California, San Diego. "Further, the voltage-dependent anion channel (VDAC1), which is also present in the outer membrane of mitochondria and controls communication between the mitochondria and the rest of the cell, has also been linked with cell death."

Professor Cleveland and colleagues built on these earlier observations and discovered that mutant SOD1 interacted with VDAC1 in the spinal cord of animals expressing mutant SOD1, and that this interaction disrupted VDAC1 function. Inhibition of VDAC1 function is known to decrease cellular energy production and drive formation of damaging reactive oxygen species.

The researchers went on to show that mutant SOD1-driven VDAC1 inhibition was seen in spinal cord mitochondria from mutant SOD1 expressing animals before symptoms developed and increased in severity during disease progression. Importantly, reduced VDAC1 activity accelerated the onset of fatal paralysis in ALS mice.

"Our evidence demonstrates that reduced VDAC1 function and correspondingly reduced mitochondrial function are direct components of intracellular damage from mutant SOD1," says Professor Cleveland. "The finding that VDAC1 is a target for mutant SOD1 within the nervous system provides important insight into the mechanism underlying premature degeneration and death of motor neurons."

The researchers include Adrian Israelson, University of California at San Diego, La Jolla, CA; Nir Arbel, Ben-Gurion University of the Negev, Beer-Sheva, Israel; Sandrine Da Cruz, University of California at San Diego, La Jolla, CA; Hristelina Ilieva, University of California at San Diego, La Jolla, CA; Koji Yamanaka, Yamanaka Research Unit, RIKEN Brain Science Institute, Saitama, Japan; Varda Shoshan-Barmatz, Ben-Gurion University of the Negev, Beer-Sheva, Israel; and Don W. Cleveland, University of California at San Diego, La Jolla, CA.


Story Source:

The above story is based on materials provided by Cell Press. Note: Materials may be edited for content and length.


Journal Reference:

  1. Adrian Israelson, Nir Arbel, Sandrine Da Cruz, Hristelina Ilieva, Koji Yamanaka, Varda Shoshan-Barmatz, Don W. Cleveland. Misfolded Mutant SOD1 Directly Inhibits VDAC1 Conductance in a Mouse Model of Inherited ALS. Neuron, 67(4) pp. 575 - 587 DOI: 10.1016/j.neuron.2010.07.019

Cite This Page:

Cell Press. "Neuron-damaging mechanism discovered in mouse model of inherited ALS." ScienceDaily. ScienceDaily, 27 August 2010. <www.sciencedaily.com/releases/2010/08/100825131538.htm>.
Cell Press. (2010, August 27). Neuron-damaging mechanism discovered in mouse model of inherited ALS. ScienceDaily. Retrieved April 17, 2015 from www.sciencedaily.com/releases/2010/08/100825131538.htm
Cell Press. "Neuron-damaging mechanism discovered in mouse model of inherited ALS." ScienceDaily. www.sciencedaily.com/releases/2010/08/100825131538.htm (accessed April 17, 2015).

Share This


More From ScienceDaily



More Health & Medicine News

Friday, April 17, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Our Love Of Puppy Dog Eyes Explained By Science

Our Love Of Puppy Dog Eyes Explained By Science

Newsy (Apr. 17, 2015) Researchers found a spike in oxytocin occurs in both humans and dogs when they gaze into each other&apos;s eyes. Video provided by Newsy
Powered by NewsLook.com
Scientists Find Link Between Gestational Diabetes And Autism

Scientists Find Link Between Gestational Diabetes And Autism

Newsy (Apr. 17, 2015) Researchers who analyzed data from over 300,000 kids and their mothers say they&apos;ve found a link between gestational diabetes and autism. Video provided by Newsy
Powered by NewsLook.com
Video Messages Help Reassure Dementia Patients

Video Messages Help Reassure Dementia Patients

AP (Apr. 17, 2015) Family members are prerecording messages as part of a unique pilot program at the Hebrew Home in New York. The videos are trying to help victims of Alzheimer&apos;s disease and other forms of dementia break through the morning fog of forgetfulness. (April 17) Video provided by AP
Powered by NewsLook.com
Boy or Girl? Intersex Awareness Is on the Rise

Boy or Girl? Intersex Awareness Is on the Rise

AP (Apr. 17, 2015) At least 1 in 5,000 U.S. babies are born each year with intersex conditions _ ambiguous genitals because of genetic glitches or hormone problems. Secrecy and surgery are common. But some doctors and activists are trying to change things. (April 17) Video provided by AP
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