Inhibiting peripheral and central MAO-B ameliorates joint inflammation and cognitive impairment in rheumatoid arthritis

• DOI: 10.1038/s12276-022-00830-z
• Publication Date: 2022-08-18T09:03:04Z
• Authors: Woojin Won; Hyun-Ji Choi; Ji-Young Yoo; Daeun Kim; Tai Young Kim; YeonHa Ju; Ki Duk Park; Hyunbeom Lee; Sang Youn Jung; C. Justin Lee
• Keywords: Inflammation; 0303 health sciences; Tumor Necrosis Factor-alpha; Fibroblasts; Article; 3. Good health; Arthritis, Rheumatoid; 03 medical and health sciences; Animals; Cognitive Dysfunction; Monoamine Oxidase; Cells, Cultured; gamma-Aminobutyric Acid

Abstract Rheumatoid arthritis (RA) is an autoimmune disorder characterized by chronic inflammation and the destruction of joints systemic organs. RA commonly accompanied neuropsychiatric complications, such as cognitive impairment depression. However, role monoamine oxidase (MAO) its inhibitors in controlling neurotransmitters associated with these complications have not been clearly identified. Here, we report that peripheral central MAO-B are highly joint RA, respectively. Ribonucleic acid (RNA) sequencing protein expression quantification were used to show related molecules, gamma aminobutyric (GABA), elevated inflamed synovium patients. In primary cultured fibroblast-like synoviocytes synovium, was significantly increased tumor necrosis factor (TNF)-α-induced autophagy, which produces putrescine, polyamine substrate for GABA synthesis. We also observed MAO-B-mediated aberrant astrocytic production augmented interleukin (IL)-1β inhibited CA1-hippocampal pyramidal neurons, responsible memory storage, animal model RA. Moreover, a newly developed reversible inhibitor ameliorated inhibiting cyclooxygenase (Cox)-2. Therefore, can be effective therapeutic target patients