A Korean research team identified the cause of cognitive impairment in rheumatoid arthritis patients and identified therapeutic targets to improve both of them 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 Cognitive and Sociality Research Center, along 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. was found to cause cognitive impairment in rheumatoid arthritis patients.
Rheumatoid arthritis is reported to be accompanied by neuropsychiatric disorders such as depression and cognitive impairment. However, the mechanism of cognitive dysfunction in rheumatoid arthritis is not clear.
The research team focused on ‘GABA’, an inhibitory neurotransmitter produced by the activation of reactive astrocyte Maobi, to induce symptoms of cognitive decline by inhibiting neuronal signal transduction. An animal model of rheumatoid arthritis with cognitive impairment analyzed. 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 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 joint inflammation by generating GABA. Then, when the selective and irreversible Maobi inhibitor ‘KSD2010’, which is currently in phase 1 clinical trial, was administered to an animal model of rheumatoid arthritis, the result of ‘one stone and two birds’ was confirmed, which reduced joint inflammation and at the same time restored 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 were not clear. .
Professor Jeong Sang-yoon of CHA Bundang 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 respect.”
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. ” he said.
The research results were published online on August 19th 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 has been selected as one of the world’s top 10 molecular medicine magazines.
By Kim Young-jun, staff reporter [email protected]
