Choline kinase: An underappreciated rheumatoid arthritis therapeutic target

Choline kinase (ChoK) has been well documented as a major enzyme involved in the anomalous cellular lipid metabolic profile of chronic inflammatory disorders. However, new research has now been unveiled that helps us to better understand how changes in lipid metabolism influence the transformational phenotype, drug resistance, and antiapoptotic characteristics of invasive cells, leading to rheumatoid arthritis (RA) disease progression. It is still unknown how ChoK modulates the lipid metabolic aberrations that may promote altered cell phenotype and functionality in RA. Herein, we review the current understanding of ChoK's role in altered metabolism in diverse cell types involved in RA progression, and for the first time, we take a step forward to complete the puzzle and summarise striking facts that link choline metabolism to its transformed phenotype, in order to postulate ChoK as a robust therapeutic target in RA. This review forms a foundation on which ChoK can be tackled as a potential biomarker, opening doors for RA diagnosis and prognosis. It frameworks several ChoK inhibitors that rewire the lipid metabolic profile in the inflammatory disease landscape and envisages its being translated to clinics. Choline Kinase - A potent therapeutic target in RA pathogenesis. Abbreviations: PI3K/AKT - Phosphatidylinositol-3-kinase/Ak strain transforming; AMPK - AMP-activated protein kinase; HIF-1α - Hypoxia-inducible factor 1. In the hypoxic arthritic environment, altered choline metabolism stimulates the hyper proliferative phenotype of synovial cells involved in the pathogenesis of RA by modulating protein cascades (PI3K/AKT, AMPK, Ras, HIF1). Phenotypic plasticity of the cells in RA leads to increased inflammation and humoral immune response, extensive angiogenesis, decreased collagen synthesis, and increased bone and cartilage degradation. Metabolomic, lipidomic, and proteomic studies help in the identification and quantification of intermediates that can act as potent therapeutic targets and as diagnostic markers in early stages of RA. [Display omitted] •The role of choline kinase in inflammatory disorders' aberrant cellular lipid metabolic profile is underlined.•The current understanding of choline kinase role in rheumatoid arthritis progression is summarized.•The importance of targeting choline kinase in rheumatoid arthritis is mentioned.•The impact of choline kinase specific inhibitors is exhibited with reference to rheumatoid arthritis.