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



Huntington’s disease is an inherited and fatal neurodegenerative disorder. A research by the scientists at Johns Hopkins Medicine, the findings of which have been published in a recent issue of  ˜Proceedings of the National Academy of Sciences', have revealed that a biochemical pathway linking oxidative stress and the amino acid cysteine in Huntington’s disease have been identified. The findings of the study provide a mechanism through which oxidative stress specifically damages nerve cells in Huntington’s disease.

Cysteine deficiency and oxidative stress are known to be playing a role in diseases like Alzheimer’s disease, arthritis, cardiovascular disease, AIDS and cancer. So, the researchers are of the opinion that the findings of this study may aid in finding therapeutic strategies for many serious conditions. There are many ways human cells regulate oxidative stress but, those involving cysteine play a central role remarked 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. Paul added that if you deplete cysteine, a majority of these antioxidant defenses will be affected.

In a previous research work, the researchers had found that the protein responsible for making cysteine, cystathionine gamma-lyase (CSE), is decreased in HD. When the levels of amino acids are low, CSE is activated by the normal cells using a protein called activating transcription factor 4 (ATF4). ATF4 tell the cell to start up the cysteine production line for protein synthesis and generation of other protective molecules derived from cysteine. Cells low in cysteine can use alternate pathways for a short time; however as time passes such cells are overwhelmed by oxidation and die. This study revealed that in Huntington disease, ATF4 is disrupted in cells which affect cysteine production.


As a part of this study, the researchers grew both healthy control brain cells and brain cells that were derived from mice with Huntington’s disease under low cysteine conditions. It was found that the healthy cells increased the activity of ATF4 under low cysteine conditions. However, in the cells from mice with Huntington’s disease they could not detect ATF4. The researchers then grew cells in conditions depleted of other amino acids and found that ATF4 levels were normal in both control and Huntington’s cells. The researchers concluded that effect was unique to cysteine which led them to wonder if elevated oxidative stress would affect the response of ATF4 because of cysteine’s role in cellular defense.

In order to find that, the researchers induced oxidative stress in healthy cells and then cut off their cysteine supply. They found that the cells’ expression of ATF4 was greatly diminished. 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 create their own cysteine.

Sbodio remarked that it is a vicious cycle – low levels of cysteine cause oxidative stress, which in turn decrease cysteine levels, thereby creating more oxidative stress which further slows cysteine production. In their previous study, the researchers’ had found that supplementing cysteine in the diets of mice exhibiting Huntington’s disease delays the progression of the disease’s symptoms. This study reveals how cysteine is regulated and how oxidative stress affects this system.

Antioxidants are known to be beneficial for health but the researchers cautioned that more information is needed on cysteine’s role in the body before researchers can confirm its therapeutic value. Too much of anything is bad – same is the case with cysteine. So, patient should abstain from self-medicating. It is always advisable to  consult a doctor before beginning any supplement.