Research could lead to advances in treatment for neurological disorders, thyroid cancer

September 23, 2013
This model shows potential binding sites on the GABA(A) receptor for cholesterol (cyan), thyroid hormone (red), and two other neurosteroids called allopregnanolone (blue) and pregnenolone sulfate (yellow).

An innovative research project at Rutgers–Camden that combines computational and experimental science is uncovering information that could lead to advances in treatments for neurological disorders and thyroid diseases.

To solve the puzzle, Rutgers–Camden professors Grace Brannigan and Joseph Martin are studying a protein fundamental to our understanding of the brain: the GABA(A) receptor.

"We're trying to determine the mechanism through which —neurosteroids and —interact with the GABA(A) receptor," says Brannigan, an assistant professor of physics in Rutgers–Camden's Center for Computational and Integrative Biology at Rutgers–Camden.

GABA is an inhibitory chemical that blocks impulses between in the brain. A GABA(A) receptor's job is to detect and respond to GABA. GABA(A) receptors are also regulated by neurosteroids, made from cholesterol, that impact behavior, stress, memory, and depression; and thyroid hormones that also affect these brain functions.

"Without a constant inhibitory effect on the brain, you could have problems like anxiety or seizures," says Martin, a professor of biology who directs the Center for Computational and Integrative Biology.

The mystery surrounds how neurosteroids and thyroid hormones work with the GABA(A) receptor. Finding the answer could lead to drug treatments for thyroid diseases, , and even learning how anesthetics work.

"We want to have a picture of what it looks like when the molecule [GABA] binds to the protein [GABA(A)]," explains Brannigan, who is predicting how they interact with each other using computer modeling. Her calculations are being made on sophisticated computers on the Rutgers–Camden campus and through the National Science Foundation's XSEDE supercomputers, which support high-end visualization and data analysis resources across the country.

Meanwhile, Martin is testing predictions about where the binding takes place by observing the response of immature frog egg cells which are made to express GABA(A) receptors.

"We're doing this high-performance simulation to determine how the two interact and where the interaction takes place," Brannigan says. "People have been trying to develop drugs that mimic these natural neurosteroids and hormones, but the synthetic versions don't seem to have the effect you'd hope."

The research could lead to an understanding of how the neurosteroids interact with the receptor, which would then impact various treatments for neurological disorders.

Explore further: GABA deficits disturb endocannabinoid system

Related Stories

GABA deficits disturb endocannabinoid system

January 24, 2012

Changes in the endocannabinoid system may have important implications for psychiatric and addiction disorders. This brain system is responsible for making substances that have effects on brain function which resemble those ...

Brain makes its own version of Valium, researchers find

May 30, 2013

Researchers at the Stanford University School of Medicine have found that a naturally occurring protein secreted only in discrete areas of the mammalian brain may act as a Valium-like brake on certain types of epileptic seizures.

Recommended for you

Artificial beta cells

December 8, 2016

Researchers led by ETH Professor Martin Fussenegger at the Department of Biosystems Science and Engineering (D-BSSE) in Basel have produced artificial beta cells using a straightforward engineering approach.

Key regulator of bone development identified

December 8, 2016

Loss of a key protein leads to defects in skeletal development including reduced bone density and a shortening of the fingers and toes—a condition known as brachydactyly. The discovery was made by researchers at Penn State ...

Researchers question lifelong immunity to toxoplasmosis

December 8, 2016

Medical students are taught that once infected with Toxoplasma gondii—the "cat parasite"—then you're protected from reinfection for the rest of your life. This dogma should be questioned, argue researchers in an Opinion ...

TET proteins drive early neurogenesis

December 7, 2016

The fate of stem cells is determined by series of choices that sequentially narrow their available options until stem cells' offspring have found their station and purpose in the body. Their decisions are guided in part by ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.