Asparagine thought essential for brain development

Research suggests the amino acid asparagine is essential for healthy brain development.

Researchers from the University of Montreal have discovered that the amino acid asparagine is essential for healthy brain development in children. However, they say that unlike other organs in the body, the brain cannot draw asparagine from dietary sources, and rather it needs the local synthesis of the amino acid to function properly.

The discovery, made by researchers at CHU Sainte-Justine and the University of Montreal, is focused on people with a specific genetic mutation that blocks asparagine metabolism. “The cells of the body can do without it because they use asparagine provided through diet. Asparagine, however, is not well transported to the brain via the blood-brain barrier,” said senior co-author of the study Dr. Jacques Michaud, who found that brain cells depend on the local synthesis of asparagine to function properly.

Foods that provide asparagine include meat, eggs and dairy products as well as aparagus, seafood, potatoes, legumes, nuts, seeds, soy and whole grains.

In April 2009, a baby in Quebec died of a rare genetic disease causing congenital microcephaly, intellectual disability, cerebral atrophy, and refractory seizures. He was the third infant to die in the family from the same disease. It led Michaud to discover the genetic abnormality responsible for this developmental disorder.

The team identified the gene affected by the mutation code for asparagine synthetase, the enzyme responsible for synthesizing the amino acid asparagine. The study is the first to associate a specific genetic variant with a deficiency of this enzyme.

“In healthy subjects, it seems that the level of asparagine synthetase in the brain is sufficient to supply neurons,” Michaud said. “In individuals with the disability, the enzyme is not produced in sufficient quantity, and the resulting asparagine depletion affects the proliferation and survival of cells during brain development.”

Children who are carriers of this mutation suffer from a variety of symptoms that can lead to death. The Quebec family lost three infant sons to this disorder. Two of their other children are alive and healthy.

“Our results not only open the door to a better understanding of the disease,” Michaud said, “but they also give us valuable information about the molecular mechanisms involved in brain development, which is important for the development of new treatments.”

Asparagine supplement could someday be given to infants to ensure an adequate level of asparagine in the brain and the latter's normal development but the geneticist explained, “The amount of supplementation remains to be determined, as well as its effectiveness.”  Likewise, since these children are already born with neurological abnormalities, it is uncertain whether this supplementation would correct the neurological deficits.

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