The hidden function of hemoglobin, a protein known for carrying oxygen and giving blood its red color, has been revealed. Its antioxidant function that protects nerve cells is now identified, suggesting a new clue for the treatment of brain diseases.
A research team led by Lee Chang-jun, Director General of the Institute for Basic Science (IBS) Cognitive and Social Research Center, along with researchers from the Korea Institute of Science and Technology (KIST) Institute of Brain Science, announced on the 22nd that they have identified the antioxidant function of hemoglobin present in astrocytes in the brain and developed low-molecular compounds to maximize this function.
Degenerative brain diseases such as amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease), Parkinson's disease, and Alzheimer's disease, as well as aging, are known to be triggered by strong oxidants known as reactive oxygen species damaging nerve cells and leading to their death. Previously developed antioxidant drugs that eliminate reactive oxygen species either failed to reach the brain or were excreted too quickly.
To overcome this limitation, the research team focused on hydrogen peroxide, a manageable reactive oxygen species. The team had previously revealed that hydrogen peroxide accumulates abnormally in reactive astrocytes, damaging surrounding nerve cells. Building on this result, they meticulously analyzed the antioxidant system within astrocytes.
As a result, they discovered that hemoglobin, which was thought to exist only in blood, is also present in the nucleolus, an organelle within astrocyte nuclei. They also identified for the first time that hemoglobin performs an antioxidant function by decomposing hydrogen peroxide into oxygen and water. This function is significantly reduced when suffering from degenerative brain diseases.
The research team developed a low-molecular compound called 'KDS12025' that can maximize the antioxidant activity of hemoglobin. This substance interacts with the iron ions within hemoglobin to facilitate the decomposition of hydrogen peroxide into oxygen and water at rates up to 100 times faster. At the same time, it also effectively passed through the brain's defenses.
The researchers administered KDS12025 to mice affected by various degenerative brain diseases to confirm its therapeutic effects. In ALS model mice, the onset of the disease and muscle weakness were delayed, extending the average survival period by more than four weeks; in the Alzheimer's model, memory retention and learning ability were restored to near-normal levels.
In aged models, the average lifespan was extended by about 30%. Some mice survived for more than three years, exceeding the original lifespan of two years. Furthermore, therapeutic effects were observed not only in brain diseases but also in systemic inflammatory diseases.
Director General Lee Chang-jun noted, "This research has newly identified the antioxidant function of hemoglobin," adding, "Unlike existing treatment strategies that supply antioxidants externally, we have proposed a new approach to treat diseases by regulating and enhancing the functions of natural proteins within our bodies." He also mentioned, "We plan to expand research so that the results of basic science lead to actual treatment strategies and drug development beyond cellular-level understanding."
The results of this study were published online on the 22nd in the international journal "Signal Transduction and Targeted Therapy."
References
Signal Transduction and Targeted Therapy (2025), DOI: https://doi.org/10.1038/s41392-025-02366-w