In neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Parkinson’s, and Alzheimer’s, healthy brain cells are damaged by aberrant reactive oxygen species (ROS). A potential treatment involves neutralizing ROS using antioxidant drugs. But these approaches failed to penetrate the brain effectively or proved unstable or indiscriminately damaged healthy cells.
Now, a new study led by scientists at the Institute for Basic Science (IBS) in Daejeon, South Korea explores how the brain defends itself against hydrogen peroxide, a particularly harmful ROS. Using advanced imaging and molecular analysis, they discovered that hemoglobin exists in the nucleolus of astrocytes, where it acts as a “pseudoperoxidase” that breaks down H₂O₂ into harmless water. Full details are published in a new Signal Transduction and Targeted Therapy paper titled “Hemoglobin as a pseudoperoxidase and drug target for oxidative stress-related diseases.”
“The key was to uncover hemoglobin’s antioxidant potential in the brain and design a ‘first-in-class’ compound that could selectively enhance it,” said Won Woojin, PhD, first author on the study. “By boosting a natural defense mechanism rather than introducing an external antioxidant, we achieved strong and lasting protection across multiple disease models associated with oxidative stress.”
According to the paper, the team developed KDS12025, a small, water-soluble molecule that binds to hemoglobin’s heme center and boosts its ability to decompose H₂O₂ by nearly 100-fold, without disrupting its normal oxygen-carrying function. Importantly, KDS12025 can cross the blood–brain barrier, making it ideal for targeting neurodegenerative disorders. Results reported in the paper indicate that in diseased astrocytes, KDS12025 sharply reduced harmful H₂O₂ levels. Furthermore, evidence collected from mouse models that ingested the molecule orally in their drinking water indicated that it had a protective effect on neurons, calmed reactive astrocytes, and restored brain function.
The researchers also tested the molecule in various animal models of disease. In mouse models of ALS and controls, mice treated with the molecule showed a delayed disease onset and lived more than four weeks longer than untreated controls. In Parkinson’s models, KDS12025 restored motor function, while in Alzheimer’s models, the molecule helped with recovering memory performance.
In aging mice, the treatment extended the median lifespan from two years to as long as three years, according to the scientists. The drug also alleviated inflammation and joint damage in a rheumatoid arthritis model. Lastly, the team found that excess H₂O₂ depletes astrocytic hemoglobin, which weakens the brain’s natural antioxidant defenses and accelerates degeneration. They showed that KDS12025 reversed this trend by boosting hemoglobin levels and activity. The result was lower oxidative stress, better neuron preservation, and more healthy brain function.
For their next steps, the team plans to study the distinct roles of α- and β-globin in the brain, refine KDS12025 derivatives for potential human use, and explore its applications in other oxidative stress–driven disorders. “This is a major step forward in the fight against neurodegenerative diseases,” said C. Justin Lee, PhD, director of the Center for Cognition and Sociality at IBS and lead author of the study. “By enhancing the brain’s own hemoglobin to combat oxidative stress, we are opening an entirely new therapeutic avenue.”
The post Boosting Hemoglobin’s Antioxidant Activity Could Counter Neurodegenerative Disorders appeared first on GEN – Genetic Engineering and Biotechnology News.
