KDS12025 enhances hemoglobin’s H2O2-decomposition, lowers oxidative stress, restores astrocyte and neuron well being, and preserves reminiscence and motor perform—remodeling a vicious cycle right into a virtuous one. Credit score: Institute for Primary Science
Hemoglobin, lengthy celebrated for ferrying oxygen in pink blood cells, has now been revealed to play an ignored—and probably game-changing—antioxidant position within the mind.
In neurodegenerative illnesses akin to amyotrophic lateral sclerosis (ALS), Parkinson’s, Alzheimer’s, and ageing, mind cells endure relentless injury from the aberrant (or extreme) reactive oxygen species (ROS). For many years, scientists have tried to neutralize ROS with antioxidant medicine, however most failed: they could not penetrate the mind successfully, had been unstable, or indiscriminately broken wholesome cells.
This new research, led by Director C. Justin Lee of the Middle for Cognition and Sociality throughout the Institute for Primary Science (IBS) in Daejeon, South Korea, got down to establish the mind’s personal defenses in opposition to a very dangerous type of ROS—hydrogen peroxide (H2O2). The research has been printed in Sign Transduction and Focused Remedy.
Utilizing superior imaging and molecular evaluation, the crew found that hemoglobin exists within the nucleolus of astrocytes—star-shaped mind cells vital for neuronal help—the place it acts as a “pseudoperoxidase,” breaking down H2O2 into innocent water.
“The key was to uncover hemoglobin’s antioxidant potential in the brain and design a ‘first-in-class’ compound that could selectively enhance it. 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,” mentioned first writer Dr. Gained Woojin.
KDS12025 delayed illness onset, restored motor perform, and prolonged lifespan from 140 to 168 days in an ALS mouse mannequin — the primary drug to realize all three. It additionally restored motor perform in Parkinson’s fashions and rescued reminiscence deficits in Alzheimer’s fashions to regular ranges. Credit score: Institute for Primary Science
The crew developed KDS12025, a small, water-soluble molecule able to crossing the blood–mind barrier. KDS12025 binds to hemoglobin’s heme heart and boosts its skill to decompose H2O2 by practically 100-fold, with out disrupting its regular oxygen-carrying perform.
In disease-like situations in astrocytes, KDS12025 sharply decreased dangerous H2O2 ranges. In mouse fashions, oral administration by means of ingesting water protected neurons, calmed reactive astrocytes, and restored mind perform.
In animal fashions, oral administration by means of ingesting water suppressed neuronal loss of life, normalized reactive astrocytes, and restored mind perform. ALS mannequin mice confirmed a delayed illness onset and lived greater than 4 weeks longer than untreated controls.
In Parkinson’s fashions, KDS12025 restored motor perform, whereas in Alzheimer’s fashions, it recovered reminiscence efficiency. In ageing mice, the therapy prolonged the median lifespan from the standard two years to so long as three years. The drug additionally alleviated irritation and joint injury in a rheumatoid arthritis mannequin.
The research additionally uncovered a dangerous suggestions loop: extra H2O2 depletes astrocytic hemoglobin, weakening the mind’s pure antioxidant defenses and accelerating degeneration. By boosting hemoglobin’s ranges and exercise, KDS12025 reversed this pattern, lowering oxidative stress, preserving neurons, and sustaining wholesome mind perform.
No earlier therapy has focused astrocytic hemoglobin as an antioxidant system, nor demonstrated such broad protecting results.
(High) Hemoglobin is current within the nucleolus of astrocytes. When astrocytic hemoglobin is knocked down, KDS12025 loses its impact, confirming that the drug’s antioxidant motion is mediated by means of astrocytic hemoglobin. (Backside) In Alzheimer’s mice, astrocytes (inexperienced, GFAP) are atrophied and hemoglobin (purple, Hbβ) is decreased, whereas KDS12025 therapy restores astrocyte morphology and hemoglobin expression. Credit score: Institute for Primary Science
“This is a major step forward in the fight against neurodegenerative diseases. By enhancing the brain’s own hemoglobin to combat oxidative stress, we are opening an entirely new therapeutic avenue,” mentioned Director Lee.
The crew now plans to additional research the distinct roles of α- and β-globin within the mind, refine KDS12025 derivatives for potential human use, and discover its purposes in different oxidative stress–pushed issues.
This work transforms hemoglobin from a well-recognized oxygen transporter right into a precision antioxidant protection system for the mind. It marks a possible paradigm shift in how scientists strategy neurodegenerative illnesses, age-related decline, and autoimmune situations.
Extra info:
Hemoglobin as a pseudoperoxidase and drug goal for oxidative stress-related illnesses, Sign Transduction and Focused Remedy (2025). DOI: 10.1038/s41392-025-02366-w
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