Exploring the therapeutic promise of targeting Rho kinase in rheumatoid arthritis

AbstractRheumatoid arthritis (RA) is a prevalent systemic autoimmune disease caused by dysregulated inflammatory reactions, T lymphocyte invasion into the joints, and articular thickening. Immune cells, primarily tumor necrosis factor-alpha (TNF- α) and chemokines (interleukin or IL-1), which are predominantly generated by activated macrophages cells, have also been involved with the pathogenesis of rheumatoid arthritis. Rho GTPases are integral factors of biochemical cascades utilized by antigens, and also by cellular receptors, cytokines, and chemokines, to modulate inflammatory reactions, according to growing data. The Rho family is a group of G proteins that govern a variety of biological and physiological activities such as mobility, actin stress fiber production, growth, and polarity. Research suggests that the Rho A and Rho-ass ociated coiled-coil kinase (ROCK) regulatory cascade could be essential in several autoimmune conditions, including RA. ROCK is activated in the synovial of rheumatoid arthritis patients, while the blocking of ROCK with fasudil could also decrease IL-6, TNF-α, and IL-1. This review covers current d evelopments in understanding the overactivation of Rho enzyme activity in RA suppressed by ROCK inhibitors which can be utilized for the treatment of autoimmune disease. We offer an outline of the function of ROCK inhibitors in immune cells and discuss findings which emphasize the rising participati on of this category of kinases within the patholog...
Source: Inflammopharmacology - Category: Drugs & Pharmacology Source Type: research