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인지 및 사회성 연구단
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Inhibiting peripheral and central MAO-B ameliorates joint inflammation and cognitive impairment in rheumatoid arthritis

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Title
Inhibiting peripheral and central MAO-B ameliorates joint inflammation and cognitive impairment in rheumatoid arthritis
Author(s)
Woojin Won; Choi, Hyun-Ji; Yoo, Ji-Young; Daeun Kim; Tai Young Kim; YeonHa Ju; Park, Ki Duk; Lee, Hyunbeom; Jung, Sang Youn; C. Justin Lee
Publication Date
2022-08
Journal
EXPERIMENTAL AND MOLECULAR MEDICINE, v.54, no.8, pp.1188 - 1200
Publisher
SPRINGERNATURE
Abstract
Rheumatoid arthritis (RA) is an autoimmune disorder characterized by chronic inflammation and the destruction of joints and systemic organs. RA is commonly accompanied by neuropsychiatric complications, such as cognitive impairment and depression. However, the role of monoamine oxidase (MAO) and its inhibitors in controlling neurotransmitters associated with these complications in RA have not been clearly identified. Here, we report that peripheral and central MAO-B are highly associated with joint inflammation and cognitive impairment in RA, respectively. Ribonucleic acid (RNA) sequencing and protein expression quantification were used to show that MAO-B and related molecules, such as gamma aminobutyric acid (GABA), were elevated in the inflamed synovium of RA patients. In primary cultured fibroblast-like synoviocytes in the RA synovium, MAO-B expression was significantly increased by tumor necrosis factor (TNF)-alpha-induced autophagy, which produces putrescine, the polyamine substrate for GABA synthesis. We also observed that MAO-B-mediated aberrant astrocytic production of GABA was augmented by interleukin (IL)-1 beta and inhibited CA1-hippocampal pyramidal neurons, which are responsible for memory storage, in an animal model of RA. Moreover, a newly developed reversible inhibitor of MAO-B ameliorated joint inflammation by inhibiting cyclooxygenase (Cox)-2. Therefore, MAO-B can be an effective therapeutic target for joint inflammation and cognitive impairment in patients with RA. Rheumatoid arthritis: Potential therapeutic target identified Inhibiting an enzyme that is upregulated during joint inflammation may prove a valuable therapy for rheumatoid arthritis (RA). As well as causing considerable pain and discomfort in the joints, RA can also trigger neuropsychiatric problems including depression and memory impairment. The monoamine oxidase (MAO) enzyme family is involved in the control of neurotransmitters, and there is evidence that links MAO-B levels with systemic inflammation. C. Justin Lee at Center for Cognition and Sociality, Institute for Basic Science,, Daejeon, South Korea, and co-workers examined the role of MAO-B in RA using patient tissue samples and mouse models. MAO-B and related molecules were upregulated in patients' inflamed joint tissues. In mice, elevated MAO-B triggered the inhibition of nerve cell activity related to memory storage. A novel drug that inhibits MAO-B reduced RA-related inflammation and cognitive impairment in mice, suggesting a promising approach to treatment.
URI
https://pr.ibs.re.kr/handle/8788114/12877
DOI
10.1038/s12276-022-00830-z
ISSN
1226-3613
Appears in Collections:
Center for Cognition and Sociality(인지 및 사회성 연구단) > 1. Journal Papers (저널논문)
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