In Portland, Oregon, scientists have captured the sharpest-ever pictures of a tiny protein in the brain that plays a key role in stroke damage. The researchers, working at Oregon Health & Science University (OHSU), used powerful microscopes to map six different shapes of a protein called ASIC1a — an acid-sensing ion channel that helps control how brain cells send signals related to learning, memory, and fear.
The team, led by Isabelle Baconguis, an assistant professor at OHSU's Vollum Institute, published their findings in the journal Nature Structural & Molecular Biology. They used a technique called cryo-electron microscopy, which fires beams of electrons at frozen proteins to create incredibly detailed 3D images. By exposing the proteins to different acid levels, the scientists were able to catch the channel in six distinct shapes.
Why does this matter? When someone has a stroke, blood flow to part of the brain gets cut off. That tissue becomes more acidic as it loses oxygen, which activates these ASIC1a channels. Once activated, they can cause serious damage to brain cells. But previous research suggests that blocking these channels could protect brain tissue from harm.
"Previous studies show that when you block this channel, it can be neuroprotective," Baconguis said. "If you're able to design a drug that delivers an inhibitor to this channel, it could lengthen tissue survival in cases of stroke."
The new images give scientists a roadmap for designing drugs that could precisely target and block this channel. Right now, researchers in Australia are already testing a molecule from spider venom that targets ASIC1a, showing promising results for improving outcomes in both heart attacks and strokes.
Baconguis noted that speed is critical when treating strokes. "The sooner you can protect brain tissue from damage, the less severe the disability stroke survivors will have," she said. "Time is of the essence when it comes to stroke." The hope is that this new structural map will help drug developers create faster, more effective treatments that could reduce disability for the millions of people who experience strokes each year.