Amino Acid Deficiency Cause of Brain Degeneration in Huntington's Disease

The loss of the ability to make the amino acid cysteine

is the cause of degeneration of the corpus striatum in rodents and people with Huntington’s disease, according to a study of genetically engineered mice.

Researchers at the Johns Hopkins University School of Medicine, led by Solomon Snyder, MD, said the disease progression slowed in mice fed a diet rich in cysteine. The study was published online March 26, 2014, in Nature.

Snyder and colleagues tracked the degenerative process to the absence of the enzyme cystathionine gamma lyase (CSE). After monitoring CSE in mouse and human brain tissue, they found considerably less of the enzyme in all diseased tissues. Mutant proteins were attaching to a crucial protein responsible for turning the CSE gene on or off, which ultimately led the diseased rodent and human brain tissue to be deprived of cysteine.

“It looked like there was a neurological deficit,” Bindu Diana Paul, PhD, a molecular neuroscientist and faculty instructor in Snyder’s laboratory said in a statement. “But nobody had looked at CSE in the brain.”

To see if loss of cysteine was directly responsible for symptoms associated with Huntington’s disease, the researchers fed mice a cysteine-rich diet.

They saw striking results in the mice, even seeing the rodents’ life expectancies increased 1 to 2 weeks after the diet was changed. Investigators are cautiously optimistic about the results but further research is needed to see if the results will be the same in humans.

The researchers noted that it is clear that the high cysteine diet merely slows but does not halt the disease in mice.

"Usually it's very hard, if not impossible, to develop straightforward mechanisms that explain what's going on in a disease,” Snyder said in a statement. “What's even harder is even if you can find a mechanism that causes a tissue to rot, usually there's nothing you can do about it. In this case, there is."