Volume 92 Issue 13 | p. 6 | News of The Week
Issue Date: March 31, 2014 | Web Date: March 27, 2014

Huntington’s Disease Could Stem From Cysteine Depletion

Neurodegeneration: Scientists finally pinpoint a mechanism for how a repeating genetic mutation might lead to the neurodegenerative disease
Department: Science & Technology | Collection: Life Sciences
News Channels: Biological SCENE
Keywords: Huntington’s Disease, cysteine
A mutated protein in Huntington’s disease depletes CSE, which converts cystathionine to cysteine.
A reaction scheme depicting the conversion of cystathionine to cysteine
A mutated protein in Huntington’s disease depletes CSE, which converts cystathionine to cysteine.

A repeating gene sequence that codes for a mutant protein in the DNA of patients with Huntington’s disease is to blame for the disorder, but how this genetic mutation causes neurodegeneration has long stymied scientists. Now a team of medical researchers led by Solomon H. Snyder at Johns Hopkins University is proposing a cellular mechanism for the disease (Nature 2014, DOI: 10.1038/nature13136).

Snyder’s theory—that the disease symptoms stem from a lack of the amino acid cysteine in the brain—is based on experiments with cultured human tissue and with mice that suffer symptoms of the disease. If proven to extend to humans in clinical trials, the theory could “decrease the onset of Huntington’s disease symptoms with a simple dietary supplementation,” comments Gavril W. Pasternak, a neuropharmacologist at Memorial Sloan Kettering Cancer Center, in New York City.

“It would be a major milestone in the understanding and treatment of the neurodegenerative disease,” Pasternak says, and would eliminate the need for “complex and risky” genetic therapy approaches that are currently the disease’s most promising treatment.

Huntington’s disease symptoms usually begin midlife, with cognitive problems, increasing loss of muscle coordination, and then dementia. Life expectancy is reduced to about 20 years after onset.

Researchers have long tried to pinpoint what the mutant Huntington’s disease protein does to brain cells but to date have only found evidence that it influences transcription. Snyder’s team showed that this mutant protein binds a transcription factor required to produce an enzyme called cystathionine γ-lyase (CSE), thus depleting the enzyme’s levels in brain cells.

Because CSE catalyzes a crucial step in the biosynthesis of cysteine, the mutation leads to an overall depletion of cysteine in brain cells. When the researchers supplemented Huntington’s mouse models with cysteine, they could reverse the disease’s characteristics.

“Since the disease is based on a very discrete genetic abnormality, the mouse model is very good,” suggesting the results could apply to humans, Snyder says. “But it makes me nervous to get people’s hopes up. We won’t know if this is a successful therapy until it is tested in clinical trials,” he cautions.

Chemical & Engineering News
ISSN 0009-2347
Copyright © American Chemical Society
Angie (Fri Mar 28 14:03:32 EDT 2014)
Thank GOD that he put Solomon H. Snyder on this planet to help figure this out! I pray for a cure everyday.
Santosh (Fri Mar 28 14:55:11 EDT 2014)
MY Uncle has Huntingtons Disease, is there any cure or Treatment?

Ch (Sun Mar 30 13:30:34 EDT 2014)
Please do as much research as possible. Our family has been devastated by this disease. So very painful to see and experience. The disease is still ripping us apart mentally, physically and emotionally. Seems nothing at all can help.
gordon thompson (Sun Mar 30 18:12:07 EDT 2014)
this sounds promising
Wayne (Wed Apr 09 21:09:05 EDT 2014)
Well, since the theory if proven correct would result in a cure being simply taking Cystenine supplements, and since Cystenine supplements are merely nutritional supplements readily available from any health store including GNC, why wait for these endless studies? People who have relatives suffering from Huntington's disease just start giving them Cystenine supplements. There's your study. Either it works, or it doesn't, but it's good for you so why not try?
Ginny Bitting (Mon Apr 28 16:54:55 EDT 2014)
We too are struggling with this disease - interestingly my husband who has HD loves yogurt and whole grains and eats a lot of them. He has been drinking smoothies with whey protein for years and has been doing far better than many expected. Of course we have no idea if it is the whey because he also has been exercising and keeping active socially, but it's good to know it might have helped.
Scott olin (Tue Aug 19 20:45:54 EDT 2014)
i take 2400 mgs of cystien 1200 before bed
600 at lunch and 600 at dinner
it works for me my symptoms are gone

I have 45 repeats
call or text 9192646222

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