Hemoglobin Antioxidant Discovery Could Transform Brain Disease Care todayheadline

The blood’s oxygen carrier may double as a brain shield. A new study from the Institute for Basic Science (IBS) in South Korea reveals that hemoglobin, long known for transporting oxygen in red blood cells, also acts as a potent antioxidant inside brain cells. By boosting this hidden function with a molecule called KDS12025, researchers restored memory and motor function in mouse models of Alzheimer’s, Parkinson’s, and ALS, extended lifespan in aging mice, and even reduced inflammation in arthritis. The findings, published in Signal Transduction and Targeted Therapy, suggest hemoglobin could become a novel drug target for neurodegeneration and beyond.

Hemoglobin’s Hidden Role In The Brain

For decades, attempts to treat neurodegenerative diseases with antioxidants have stumbled because drugs often failed to cross the blood–brain barrier or disrupted healthy signaling. The IBS team, led by Director C. Justin Lee, instead looked inside the brain itself. They discovered that astrocytes, star-shaped support cells, naturally produce hemoglobin within their nuclei. There, it breaks down hydrogen peroxide (H2O2), a reactive molecule that drives oxidative stress and neuronal damage.

When excess H2O2 overwhelms the system, astrocytic hemoglobin levels fall, fueling a vicious cycle of oxidative damage and cell death. By enhancing hemoglobin’s protective activity, researchers found a way to break that cycle.

“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 first author Dr. Woojin Won in the IBS release.

A First-In-Class Enhancer: KDS12025

The team developed KDS12025, a small, water-soluble molecule that easily crosses the blood–brain barrier. It binds to hemoglobin’s heme center and increases its H2O2-decomposition ability nearly 100-fold, without affecting oxygen transport. In mice, the compound was given orally in drinking water and showed broad protective effects:

• ALS model mice lived more than four weeks longer and had delayed disease onset.
• Parkinson’s model mice regained motor function.
• Alzheimer’s model mice recovered memory performance.
• Aging mice lived up to 50 percent longer and retained youthful motor ability.
• In a rheumatoid arthritis model, joint inflammation and damage were significantly reduced.

Breaking A Vicious Cycle

The study highlights how oxidative stress depletes astrocytic hemoglobin, which in turn weakens the brain’s own antioxidant defenses. KDS12025 reversed this process, restoring hemoglobin levels and function. This dual action preserved neurons and maintained brain health across different disease models.

Notably, gene-silencing experiments confirmed that hemoglobin beta (Hbβ) in astrocytes was required for the drug’s effects. Without it, KDS12025 lost its protective power.

Key Findings

• Sample and scope: Mouse models of Alzheimer’s, Parkinson’s, ALS, aging, and rheumatoid arthritis.
• Intervention: Oral administration of KDS12025 in drinking water at low daily doses.
• Main effects: Reduced oxidative stress, restored astrocytic hemoglobin, preserved neurons, and improved memory and motor function.
• Lifespan: Aging mice lived up to three years, compared to two years for untreated controls.
• Safety: KDS12025 enhanced hemoglobin’s antioxidant activity without impairing its oxygen-carrying role or metabolism.
• Location: Research conducted at the Institute for Basic Science in Daejeon, South Korea.

Implications And Next Steps

These findings reframe hemoglobin from a familiar oxygen transporter into a precision antioxidant system within the brain. If replicated in humans, therapies based on KDS12025 or similar compounds could offer broad-spectrum protection against diseases rooted in oxidative stress, including neurodegeneration, aging, and autoimmune disorders.

Director Lee and his team plan to refine KDS12025 derivatives for human trials and to explore the distinct contributions of alpha- and beta-globin in the brain. Their work points toward a future where the body’s own oxygen-carrying protein becomes a tool to fight some of the most intractable diseases of the nervous system.

Takeaway

Researchers discovered that hemoglobin in brain astrocytes acts as an antioxidant defense against hydrogen peroxide. By enhancing this function with the molecule KDS12025, they restored brain health and extended lifespan in mice. The work establishes hemoglobin as a novel therapeutic target for Alzheimer’s, Parkinson’s, ALS, aging, and autoimmune conditions.

Journal: Signal Transduction and Targeted Therapy
DOI: 10.1038/s41392-025-02366-w