Grants:

Signaling pathways affecting human TRPC5 receptor function: Prediction of their association with rheumatoid arthritis pain

Grant agency: GACR
Identification number of grant: 22-13750S
Head of the project: RNDr. Viktorie Vlachová, DrSc. (Fyziologický ústav AV ČR, v. v. i.)
Vice-head of the project: RNDr. Ivan Barvík Jr., PhD., Tomáš Soukup ()

Rheumatoid arthritis (RA) is a painful systemic autoimmune disease severely afflicting around 1% of the worldwide population. The genetic profile of RA patients emerges as a key determinant of therapeutic efficacy and a number of gene polymorphisms associated with RA related signaling pathways have been identified. Recently, genetic or pharmacological blockage of transient receptor potential canonical 5 (TRPC5) has been shown to amplify joint inflammation and hyperalgesia in human and murine models of RA; however, the cellular mechanisms await elucidation. Using a combination of molecular biology, microscopy, electrophysiology, and molecular modeling, this project aims to (i) screen for fundamental cellular mechanisms regulating human TRPC5 channel, (ii) genotype single nucleotide polymorphisms along the intracellular pathways involved in RA with the aim to clarify the putative role of TRPC5 as the target channel, and to (iii) characterize the molecular mechanisms through which TRPC5 may contribute to the pathogenesis of rheumatoid arthritis pain and inflammation.