Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New evidence: How amino acid cysteine combats Huntington's disease

27.07.2016

Study clarifies tie between cysteine deficiency and Huntington's disease

Researchers at Johns Hopkins Medicine report they have identified a biochemical pathway linking oxidative stress and the amino acid cysteine in Huntington's disease. The findings, described in last week's issue of the Proceedings of the National Academy of Sciences, provide a mechanism through which oxidative stress specifically damages nerve cells in Huntington's disease, an inherited and fatal neurodegenerative disorder.


This is an image of a rodent neuron shown in green.

Credit: Gerry Shaw via Wikimedia

Because cysteine deficiency and oxidative stress have been linked to other diseases, such as Alzheimer's disease, arthritis, cardiovascular disease, AIDS and cancer, the investigators say these findings may facilitate therapeutic strategies for many serious conditions.

Researchers Juan Sbodio, Ph.D.; Solomon Snyder, M.D., Ph.D., D.Sc.; and Bindu Paul, Ph.D., all of the Johns Hopkins University School of Medicine's Solomon H. Snyder Department of Neuroscience, say that while there are many ways human cells regulate oxidative stress, those involving cysteine play a central role. "If you deplete cysteine, you will affect a majority of these antioxidant defenses," says Paul.

The researchers' past experiments in mice, published in the May 2014 issue of Nature, showed that the protein responsible for making cysteine, cystathionine gamma-lyase (CSE), is depleted in HD. When amino acids levels are low, normal cells will activate CSE using a protein called activating transcription factor 4 (ATF4).

ATF4 recognizes the DNA sequences that code for proteins involved in amino acid synthesis, including CSE, and tell the cell to start up the cysteine production line for protein synthesis and generation of other protective molecules derived from cysteine. While cells deficient in cysteine can use alternate pathways for a short time, such cells are eventually overwhelmed by oxidation and die. In this study, researchers discovered that ATF4 is disrupted in cells with Huntington's disease, affecting cysteine production.

To characterize this pathway, researchers grew both healthy control brain cells and brain cells derived from mice with Huntington's disease under low cysteine conditions. They found that while the healthy cells increased the activity of ATF4 under low cysteine conditions, they could not detect ATF4 in the cells from mice with Huntington's disease.

This effect was unique to cysteine: When the researchers grew cells in conditions depleted of other amino acids, ATF4 levels were normal in both control and Huntington's cells. "That intrigued us, and we wondered if elevated oxidative stress would affect the response of ATF4 because of cysteine's role in cellular defense," Paul says.

To test this, the researchers induced oxidative stress in healthy cells by exposing them to hydrogen peroxide, a strong oxidizing agent, and then cutting off their cysteine supply. Under these conditions, the cells' expression of ATF4 was greatly reduced. Conversely, when Huntington's cells were grown in cysteine-depleted conditions but given an antioxidant, vitamin C, the cells regained their ability to create ATF4 and make their own cysteine.

"These findings implicate a vicious cycle where low levels of cysteine cause oxidative stress, which leads to decreased cysteine levels, therefore creating more oxidative stress, further slowing cysteine production," says Sbodio. The researchers' previous studies showed that supplementing cysteine in the diets of mice exhibiting Huntington's disease delays the progression of the disease's symptoms. The present study reveals the mechanisms through which cysteine is regulated and how oxidative stress affects this system.

Paul and her colleagues note that antioxidants have long been noted as beneficial for promoting health, but they caution that while antioxidants can mitigate disease symptoms in the lab, much more information on cysteine's role in the body is needed before researchers can confirm its therapeutic value. In fact, the researchers pointed out that supplementing with too much cysteine could be harmful. Paul says that for some conditions, there may be benefits, but people should "always consult their doctor before beginning any supplement. We don't want patients to self-medicate."

###

This study was funded by grants from the National Institute of Mental Health (MH18501) and the CHDI Foundation.

Rachel Butch | EurekAlert!

More articles from Health and Medicine:

nachricht Norovirus evades immune system by hiding out in rare gut cells
12.10.2017 | University of Pennsylvania School of Medicine

nachricht Flexible sensors can detect movement in GI tract
11.10.2017 | Massachusetts Institute of Technology

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Ocean atmosphere rife with microbes

17.10.2017 | Life Sciences

Neutrons observe vitamin B6-dependent enzyme activity useful for drug development

17.10.2017 | Life Sciences

NASA finds newly formed tropical storm lan over open waters

17.10.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>