Research Team Led by Changjun Lee at the Institute for Basic Science
[Asia Economy Reporter Kim Bong-su] The cause of cognitive impairment observed in patients with rheumatoid arthritis has been identified.
The Institute for Basic Science (IBS) announced on the 26th that the research team led by Lee Chang-jun, head of the Cognitive and Sociality Research Center, in collaboration with Professor Jeong Sun-yoon of the Rheumatology Department at Bundang CHA Hospital, discovered that the enzyme "MAO-B" in reactive astrocytes in the brain induces cognitive impairment in rheumatoid arthritis patients. They also confirmed that inhibiting this MAO-B not only restores cognitive function but is also effective in alleviating joint inflammation simultaneously.
Rheumatoid arthritis is a common autoimmune disease often thought of simply as a condition causing joint inflammation, but it has been reported to be accompanied by neuropsychiatric disorders such as depression and cognitive impairment. However, the mechanism behind cognitive dysfunction in rheumatoid arthritis has not been clearly understood.
The research team focused on the inhibitory neurotransmitter GABA, produced by MAO-B activity in reactive astrocytes, which suppresses neuronal signaling and causes cognitive decline symptoms. They analyzed an animal model of rheumatoid arthritis accompanied by cognitive impairment. As a result, they confirmed that interleukin-1 beta (IL-1β), an inflammatory substance found systemically, affects astrocytes in the hippocampus of the brain, causing excessive GABA production by MAO-B, which leads to cognitive impairment.
Additionally, analysis of "synovial cells" isolated from the joint tissues of rheumatoid arthritis patients revealed that MAO-B, known to be primarily expressed in astrocytes in brain cells, is also present in synovial cells in the joints and is expressed proportionally to the degree of inflammation. They also confirmed that MAO-B in synovial cells generates GABA and is involved in joint inflammation.
Furthermore, when the selective and irreversible MAO-B inhibitor "KSD2010," currently in phase 1 clinical trials, was administered to the rheumatoid arthritis animal model, a reduction in joint inflammation and simultaneous recovery of cognitive function were observed. This experimentally demonstrated that MAO-B in brain astrocytes and synovial cells in joints is an effective therapeutic target with a "two birds with one stone" effect, improving cognitive impairment and alleviating joint inflammation.
This research was published on May 19 in the official journal of the Korean Society for Biochemistry and Molecular Biology, Experimental & Molecular Medicine (IF=12.153).
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