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 Laser activated gold pyramids could deliver drugs, DNA into cells without harm
24.03.2017 | Harvard John A. Paulson School of Engineering and Applied Sciences

nachricht What does congenital Zika syndrome look like?
24.03.2017 | University of California - San Diego

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: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Argon is not the 'dope' for metallic hydrogen

24.03.2017 | Materials Sciences

Astronomers find unexpected, dust-obscured star formation in distant galaxy

24.03.2017 | Physics and Astronomy

Gravitational wave kicks monster black hole out of galactic core

24.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>