Ferroptosis in Rheumatoid Arthritis: A Potential Therapeutic Strategy

Abstract

Ferroptosis is one of the newly discovered forms of cell-regulated death characterized by iron-dependent lipid peroxidation. Extensive research has focused on the roles of ferroptosis in tumors, blood diseases, and neurological diseases. Some recent findings have indicated that ferroptosis may also be related to the occurrence and development of inflammatory arthritis. Ferroptosis may be a potential therapeutic target, and few studies in vitro and animal models have shown implications in the pathogenesis of inflammatory arthritis. This mini review discussed the common features between ferroptosis and the pathogenesis of rheumatoid arthritis (RA), and evaluated therapeutic applications of ferroptosis regulators in preclinical and clinical research. Some critical issues worth paying attention to were also raised to guide future research efforts.

The Role of Reactive Oxygen Species in the Rheumatoid Arthritis-Associated Synovial Microenvironment

“…Iron is found in the synovial membrane of lesions and is known to be a catalyst for H 2 O 2 production of • OH via the Fenton reaction [ 38 ]. The degenerative process of RA development may be aided by lipid peroxidation-related ferroptosis [ 39 , 40 ]. Notably, sulfasalazine indirectly increases ferric iron levels, triggering the Fenton reaction, which produces excess lipid ROS and causes ferroptosis [ 41 ].…”

Bromodomains in Human-Immunodeficiency Virus-Associated Neurocognitive Disorders: A Model of Ferroptosis-Induced Neurodegeneration

“…Interestingly, recent studies in patients with rheumatoid arthritis (RA) showed that prolonged treatment with CQ and HCQ decreased the risk of Parkinson’s disease (PD), indicating anti-neurodegenerative properties ( Paakinaho et al, 2022 ). Indeed, as CQ and HCQ inhibit CatB, a protein implicated in the pathogenesis of both RA and PD, it is likely that these drugs inhibit CatB ( Hashimoto et al, 2001 ; Tsujimura et al, 2015 ; Mahoney-Sánchez et al, 2021 ; Zhao et al, 2022 ).…”

Iron supplementation aggravates joint inflammation in mice with acute gouty arthritis

“…However, iron overload is a necessary condition to induce ferroptosis in cells, and ferroptosis plays an important role in the pathogenesis of inflammatory joint diseases such as rheumatoid arthritis. 15 It is a great pity that this study has not yet provided additional validation of the results by iron chelating therapy. In the next studies, we will investigate through more experiments whether iron overload or ferroptosis in cells is involved in the pathogenesis of AGA and how to induce or aggravate joint inflammation.…”