IBS discovers a therapeutic target to simultaneously improve cognitive impairment and arthritis

A Korean research team has identified the cause of cognitive impairment in rheumatoid arthritis patients and identified therapeutic goals to improve both at the same time.

At the Institute of Basic Science (IBS, President Noh Do-young) under the Ministry of Science and ICT, Chang-Jun Lee, a team from the Cognitive and Sociality Research Center, together with Professor Sang-Yoon Sang-Yoon of the Department of Rheumatology at CHA Bundang Hospital (Director Jae-Hwa Kim), collaborated with the “MAO-B” enzyme in reactive stellate cells in the brain. It has been found to cause cognitive impairment in patients with rheumatoid arthritis.

Rheumatoid arthritis is said to be accompanied by neuropsychiatric disorders such as depression and cognitive impairment. However, the mechanism of cognitive dysfunction in rheumatoid arthritis is unclear.

The research team focused on ‘GABA’, an inhibitory neurotransmitter produced by the activation of the reactive Maobi astrocyte, to induce symptoms of cognitive decline by inhibiting neuronal signal transduction. An animal model of rheumatoid arthritis with cognitive impairment was analyzed. As a result, it has been confirmed that “interleukin-1beta (IL-1β)”, an inflammatory substance found throughout the body, affects astrocytes in the hippocampus in the brain and that excess GABA produced by Maobi causes cognitive impairment. .

Furthermore, as a result of the analysis of “synovial cells” isolated from the joint tissues of patients with rheumatoid arthritis, it has been confirmed that Maobi also exists in the synovial cells (cells that drain joint fluid) of the joints and is involved in joint inflammation generating GABA. Then, when the selective and irreversible Maobi inhibitor “KSD2010”, currently in phase 1 clinical trial, was administered to an animal model of rheumatoid arthritis, the result of “one honeycomb and two birds” was confirmed, which resulted in reduced joint inflammation and restored cognitive function at the same time.

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Woojin Won, a researcher at IBS, said: “Until now, research in rheumatoid arthritis has focused on the inflammatory mechanism, so the cause and goal of treating cognitive impairment were unclear.

Professor Jeong Sang-yoon of CHA Bundang Hospital said: “This study revealed the mechanism of cognitive impairment such as forgetfulness and memory loss complained by rheumatoid arthritis patients at the actual treatment site. It is of great importance to that. regard”.

Chang-Jun Lee, head of IBS, said: “We have presented for the first time the mechanism by which cognitive impairment in rheumatoid arthritis is induced by reactive astrocytes caused by chronic inflammation.”

The research results were published online Aug.19 in ‘Experimental Molecular Medicine (IF = 12,153)’, an official journal of the Korean Society of Biochemical and Molecular Biology, which is a sister journal of Nature and was selected as one of the 10 best molecular medicine journals.

By Kim Young-jun, staff reporter [email protected]

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