A Korean research team identified the cause of cognitive impairment in rheumatoid arthritis patients and identified therapeutic targets 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 at the Center for Cognitive and Social Research, together with Professor Sang-Yoon Sang-Yoon of the Department of Rheumatology at Bundang CH Hospital (Director Jae-Hwa Kim), collaboration with the enzyme ‘MAO-B’ in reactive stellate cells in the brain was found to cause cognitive impairment in rheumatoid arthritis patients.
Neuropsychiatric disorders such as depression and cognitive impairment are said to accompany rheumatoid arthritis. However, the mechanism of cognitive dysfunction in rheumatoid arthritis is not clear.
The research team focused on ‘GABA’, an inhibitory neurotransmitter produced by reactive Maobi astrocyte activation, to induce symptoms of cognitive decline by inhibiting neuronal signal transmission. An animal model of rheumatoid arthritis with cognitive impairment was analysed. As a result, it was confirmed that ‘interleukin-1beta (IL-1β)’, an inflammatory substance found throughout the body, affects astrocytes in the hippocampus in the brain, and that GABA overproduced by Maobi causes cognitive impairment.
In addition, as a result of analyzing ‘synovial cells’ isolated from the joint tissues of rheumatoid arthritis patients, it was confirmed that Maobi also exists in synovial cells (cells that drain joint fluid) in the joints and is involved in inflammation jointly by producing GABA . Then, when the selective and irreversible Maobi inhibitor ‘KSD2010’, currently in a phase 1 clinical trial, was given to an animal model of rheumatoid arthritis, the ‘one stone and two birds’ result was confirmed, reducing joint inflammation and at the same time restore cognitive function.
Woojin Won, a researcher at IBS, said, “Until now, research on rheumatoid arthritis has focused on the inflammatory mechanism, so the cause and treatment target of cognitive impairment was not clear.
Professor Jeong Sang-yoon of Bundang CHA Hospital said, “This study revealed the mechanism of cognitive impairment such as forgetfulness and memory loss complained of by rheumatoid arthritis patients at the actual treatment site. It is of great significance in 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 caused by reactive astrocytes caused by chronic inflammation,” he said.
The results of the research were published online on August 19th in ‘Experimental Molecular Medicine (IF=12.153)’, the official journal of the Korean Society of Biochemical and Molecular Biology, which is a sister journal to Nature and has been selected as one of the books of the world. Top 10 molecular medicine journals.
By Kim Young-jun, staff reporter kyj85@etnews.com
