New Clues Found on Mechanism for Chronic Neurological Disorder (2009.3.19)
Korean scientists have identified the structure of a protein linked to epilepsy and other brain function abnormalities, which they say could present new opportunities in treatment and drug development.
In a study published by peer-review European Molecular Biology Organization (EMBO) Journal, a team of researchers led Kim Kyung-jin of Pohang University of Science and Technology (POSTECH) presented the crystal structure of the succinic semialdehyde dehydrogenase (SSADH) protein.
SSADH deficiency has been associated with epilepsy and other neurological conditions, and understanding the structure of the protein provides an important clue in revealing the mechanism of how they develop, Kim said.
One out of every 200 people suffers from epilepsy, and the over-expression of gamma-aminobutyric acid (GABA), the most abundant inhibitory neurotransmitter in the brain, has been cited among the main causes for epileptic seizures.
In healthy individuals, GABA is converted to succinic semialdehyde (SSA) by GABA transaminase (GABA-T), and SSA is then converted to succinic acid by the SSADH protein.
Thus, the deficiency of SSADH, which results in an up-regulation of GABA levels in the brain, has been pointed to as the cause for nerve cells in the brain becoming overly active, but there has been little research on what causes SSADH functions to deteriorate.
Using the 6C1 beam-line at POSTECH’s accelerator laboratory to unveil SSADH’s crystal structure, Kim found that SSADH loses its ability to interact with SSA when it becomes oxidized by reactive oxygen.
“The over-expression of GABA has been linked to epilepsy and other conditions such as speech disorders and mental retardation, and identifying a link between GABA levels and reactive oxygen is a significant achievement,” Kim said.
“We believe that our findings could give us the core technology to achieve breakthroughs in drug development.”