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KMID : 0620920220540081188
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Experimental & Molecular Medicine
2022 Volume.54 No. 8 p.1188 ~ p.1200
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Inhibiting peripheral and central MAO-B ameliorates joint inflammation and cognitive impairment in rheumatoid arthritis
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Won Woo-Jin
Choi Hyun-Ji
Yoo Ji-Young
Kim Da-Eun
Kim Tai-Young
Ju Yeon-Ha
Park Ki-Duk
Lee Hyun-Beom
Jung Sang-Youn
Lee C. Justin
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Abstract
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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)-α-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)-1β 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.
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KEYWORD
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Astrocyte, Rheumatoid arthritis
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