Press Release
HKBU finds specific enzyme harmful to brain function, paving way for treatments targeting cognitive impairment and neurodegenerative diseases
Tuesday, 10 February 2026
A research team led by Hong Kong Baptist University (HKBU) has made a breakthrough by discovering, for the first time, that pharmacologically inhibiting an enzyme in the brains of mice can restore memory and reverse cognitive deficits caused by ageing and obesity. This discovery paves the way for novel drug treatments targeting cognitive impairment and neurodegenerative diseases in humans.
Previous studies have suggested ageing and obesity are associated with heightened neuroinflammation, which can lead to dysfunction of the hippocampus, the brain’s memory centre, including memory loss and other cognitive deficits. Efforts were made to explore ways to reduce neuroinflammation. However, the results are not satisfactory as, to a large extent, neuroinflammation is only one of the contributors to cognitive decline.
A research team led by Professor Xavier Wong Hoi-leong, Professor of the Teaching and Research Division of the School of Chinese Medicine at HKBU, has found that in both mice and humans, neuroinflammation responses increase the activation of the enzyme membrane type 1 matrix metalloproteinase (MT1-MMP) in the hippocampus. Consistent with this, they also found that activating hippocampal MT1-MMP alone can trigger memory and cognitive decline in mice, even when there is no change in the neuroinflammation.
The researchers genetically blocked MT1-MMP or reduced the MT1-MMP levels in the mouse models and assessed their memory and learning with multiple tests. The results showed that aged mice with reduced MT1-MMP levels performed comparably to young mice. The researchers also found that treatment with a chemical inhibitor targeting MT1-MMP improved the learning and memory of aged mice without detectable toxicity.
The team further tested the MT1-MMP chemical inhibitor in obese mice. The results showed improvements in both learning and memory. These findings suggest that MT1-MMP is a promising therapeutic target for cognitive decline associated with ageing and obesity.
The researchers also unveiled the mechanism by which MT1-MMP impairs brain function. They found that MT1-MMP cleaves a receptor called GPR158 in the hippocampus. When these receptors are damaged, osteocalcin - a protein important for maintaining memory and cognitive function - cannot function effectively, thereby affecting learning and memory.
The findings of the HKBU research team have been published in the international scientific journal Cell Discovery. Professor Xavier Wong said: “Our study demonstrates, for the first time, that cognitive impairment in ageing and obesity is driven by a mechanism centred on MT1-MMP. The MT1-MMP inhibitors can effectively improve cognitive dysfunctions without any signs of toxicity, highlighting the potential to develop safe and effective pharmaceutical therapies. Our collective research findings position MT1-MMP as a promising therapeutic target for a range of age-related diseases, including neurodegeneration, obesity, diabetes, and atherosclerosis.”
Looking ahead, the research team is working to advance MT1-MMP inhibitors into clinical development, providing new therapeutic options for patients experiencing cognitive decline due to ageing, obesity, or related conditions.
-End-
