New Insights into Hemoglobin’s Protective Role in Brain Cells Suggest Promising Therapeutic Strategies

Recent research has uncovered a groundbreaking function of hemoglobin beyond its well-known role in oxygen transport: acting as a natural antioxidant in brain cells. Traditionally recognized for ferrying oxygen through red blood cells, hemoglobin is now identified to reside within the nucleolus of astrocytes—star-shaped support cells in the brain—and serve as a 'pseudoperoxidase.' This enzyme-like activity enables hemoglobin to decompose hydrogen peroxide (H₂O₂), a reactive oxygen species (ROS) that contributes to neuronal damage in neurodegenerative diseases.

In conditions such as Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis (ALS), and during aging, brain cells grapple with oxidative stress caused by excess ROS. Conventional antioxidant drugs have struggled to achieve therapeutic effectiveness due to poor brain penetration, instability, or non-specific actions. The discovery that hemoglobin can naturally mitigate oxidative stress within brain cells opens new therapeutic avenues.

Led by Director C. Justin Lee at the Institute for Basic Science in South Korea, the study employed advanced imaging and molecular analytics to reveal that hemoglobin's presence in astrocytes' nucleolus functions as a crucial defense mechanism. The team developed a novel molecule, KDS12025, which can cross the blood-brain barrier and enhances hemoglobin's ability to decompose H₂O₂ by almost 100 times without impairing its oxygen-carrying role.

In various disease models, oral administration of KDS12025 reduced harmful H₂O₂ levels, protected neurons, decreased reactive astrocyte activation, and restored normal brain functions. Notably, in ALS mouse models, treatment delayed disease onset by several weeks and extended lifespan. Similar protective effects were observed in Parkinson’s and Alzheimer’s models, including the improvement of motor skills and memory. The treatment also extended lifespan in aging mice and alleviated inflammation and joint issues in rheumatoid arthritis models.

A key finding was the identification of a damaging feedback loop: excess H₂O₂ depletes astrocytic hemoglobin, weakening the brain’s antioxidant defenses and accelerating neurodegeneration. Boosting hemoglobin levels and activity through KDS12025 breaks this cycle, reduces oxidative damage, and maintains neural health.

This pioneering research positions astrocytic hemoglobin as a vital, endogenous antioxidant system and introduces a new class of therapeutic agents targeting oxidative stress. Future studies aim to distinguish the roles of different globin types in the brain, refine drug derivatives for human application, and explore potential benefits in other oxidative stress-related disorders.

Overall, these findings transform our understanding of hemoglobin from a simple oxygen transporter to an essential neuroprotective agent, offering promising strategies for combating neurodegenerative diseases, aging, and related conditions.

source: https://medicalxpress.com/news/2025-08-hemoglobin-antioxidant-role-brain-cells.html