Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Key brain antioxidant linked to Alzheimer’s and Parkinson’s

15.12.2005


EAAC1 protein is the main transporter of cysteine into neurons, providing vital antioxidant protection



A study conducted at the San Francisco VA Medical Center has identified a protein found in both mice and humans that appears to play a key role in protecting neurons from oxidative stress, a toxic process linked to neurodegenerative illnesses including Alzheimer’s and Parkinson’s diseases.

The study, led by Raymond Swanson, MD, chief of neurology and rehabilitation services at SFVAMC, identified the protein – known as EAAC1 in mice and as EAAT3 in humans – as the main mechanism through which the amino acid cysteine is transported into neurons. Cysteine is an essential component of glutathione, which Swanson terms "the most important antioxidant in the brain."


It had been thought previously that the main function of the protein was to remove excess glutamate, a neurotransmitter, from brain cells.

"It’s known that neurons don’t take up cysteine directly, and it’s never been clear exactly how it gets there," says Swanson, who is also professor and vice chair of neurology at the University of California, San Francisco. "This study provides the first evidence that EAAC1 is the mechanism by which cysteine gets into neurons – and that transporting cysteine is probably its chief function."

Study findings are currently available in the Advance Online Publication section of Nature Neuroscience.

Antioxidants such as glutathione provide protection from oxidative stress, which kills cells through the "uncontrolled reaction of lipids in the cells with oxygen--basically, burning them out," says Swanson. Since the brain uses a lot of oxygen and is "chock full of lipids," it is particularly vulnerable to oxidative stress, he notes.

In the first part of the study, Swanson and his co-authors observed a colony of mice deficient in the gene responsible for the production of EAAC1 and compared their behavior with that of a colony of normal, or "wild type," mice. They noticed that around the age of 11 months – old age for a mouse – the gene-deficient mice began to act listlessly, not groom themselves properly, and exhibit other signs of senility. In contrast, the wild type mice "looked and acted totally normal," according to Swanson.

Then, in postmortem examination, the researchers found that the brains of the EACC1-deficient mice had abnormally enlarged ventricles – openings within the brain that provide a path for cerebrospinal fluid – while the ventricles of the wild type mice were normal. Enlarged ventricles "also occur in Alzheimer’s patients," Swanson notes.

In addition, it was found that the EAAC1-deficient brains had fewer neurons in the hippocampus, and that all neurons in the hippocampus and cortex showed evidence of oxidative stress, unlike in the wild type mice.

The researchers then compared brain slices from younger mice in both groups. They found that it took ten times less hydrogen peroxide – a powerful oxidant – to kill slices from the EAAC1-deficient mice than it took to kill slices from the normal mice. This demonstrated that brains of mice unable to produce EAAC1 were ten times as vulnerable to oxidative stress as mice with the ability to produce EAAC1.

The researchers also found that the neurons of the EAAC1-deficient mice contained lower levels of the antioxidant glutathione compared to those of the normal mice.

Taken together, these results "support the idea that oxidative stress contributes to aging" in the brain, a well-known concept that Swanson calls "appealing," but difficult to prove or disprove. "This certainly adds credence to the idea," he says.

In the final part of the study, Swanson and his team investigated whether oxidative stress in EAAC1-deficient mice might be reversible.

For several days, a group of gene-deficient mice were fed N-acetylcysteine, an oral form of cysteine that is readily taken up by neurons. When their neuron slices were compared with slices from untreated gene-deficient mice, it was found that N-acetylcysteine "had completely corrected the biochemical defect" in their neurons, recounts Swanson. "Their glutathione levels were normal, their ability to withstand hydrogen peroxide toxicity was normal, and the oxidants we saw in the neurons in response to oxidative challenges were normal."

Based on the results of the current study, Swanson and his group are working to determine whether EAAC1 expression is altered in neurodegenerative illnesses such as Alzheimer’s and Parkinson’s diseases. Should this prove to be the case, says Swanson, then manipulation of EAAC1 levels "might provide a novel approach" to the treatment of these diseases in the future.

Steve Tokar | EurekAlert!
Further information:
http://www.ncire.org
http://www.ucsf.edu

More articles from Life Sciences:

nachricht Bioenergy cropland expansion could be as bad for biodiversity as climate change
11.12.2018 | Senckenberg Forschungsinstitut und Naturmuseen

nachricht How glial cells develop in the brain from neural precursor cells
11.12.2018 | Universitätsmedizin der Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Topological material switched off and on for the first time

Key advance for future topological transistors

Over the last decade, there has been much excitement about the discovery, recognised by the Nobel Prize in Physics only two years ago, that there are two types...

Im Focus: Researchers develop method to transfer entire 2D circuits to any smooth surface

What if a sensor sensing a thing could be part of the thing itself? Rice University engineers believe they have a two-dimensional solution to do just that.

Rice engineers led by materials scientists Pulickel Ajayan and Jun Lou have developed a method to make atom-flat sensors that seamlessly integrate with devices...

Im Focus: Three components on one chip

Scientists at the University of Stuttgart and the Karlsruhe Institute of Technology (KIT) succeed in important further development on the way to quantum Computers.

Quantum computers one day should be able to solve certain computing problems much faster than a classical computer. One of the most promising approaches is...

Im Focus: Substitute for rare earth metal oxides

New Project SNAPSTER: Novel luminescent materials by encapsulating phosphorescent metal clusters with organic liquid crystals

Nowadays energy conversion in lighting and optoelectronic devices requires the use of rare earth oxides.

Im Focus: A bit of a stretch... material that thickens as it's pulled

Scientists have discovered the first synthetic material that becomes thicker - at the molecular level - as it is stretched.

Researchers led by Dr Devesh Mistry from the University of Leeds discovered a new non-porous material that has unique and inherent "auxetic" stretching...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

New Plastics Economy Investor Forum - Meeting Point for Innovations

10.12.2018 | Event News

EGU 2019 meeting: Media registration now open

06.12.2018 | Event News

Expert Panel on the Future of HPC in Engineering

03.12.2018 | Event News

 
Latest News

Electronic evidence of non-Fermi liquid behaviors in an iron-based superconductor

11.12.2018 | Physics and Astronomy

Topological material switched off and on for the first time

11.12.2018 | Materials Sciences

NIST's antenna evaluation method could help boost 5G network capacity and cut costs

11.12.2018 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>