HSP90: A potential drug target in inflammatory skin diseases

Abstract

Heat shock protein 90 (HSP90) is a chaperone protein belonging to the HSP family. HSP90 modulates clients by stabilising, folding, maturing, and tagging clients for proteasomal degradation. Several clients of HSP90 are involved in cancer development and HSP90 is required for some oncoproteins, making HSP90 a potential target in anticancer treatment. Recently HSP90 has also been suggested as a potential drug target in inflammatory skin diseases based on both in vitro and in vivo studies in animal models and human clinical trials. The role of HSP90 in blistering skin diseases has been studied in vitro, ex vivo, and in vivo using animal models. Human clinical studies investigating HSP90 inhibition in psoriasis and hidradenitis suppurativa have either been conducted or are ongoing and in vitro and ex vivo studies have investigated the role of HSP90 in systemic lupus erythematosus and diffuse cutaneous systemic sclerosis. Here, we review the current literature investigating the role of HSP90 in these diseases.

Heat shock protein 90 (Hsp90) inhibitor STA-9090 (Ganetespib) ameliorates inflammation in a mouse model of atopic dermatitis

“…Recently, due to its pleiotropic activity, Hsp90 has become the subject of interest for many researchers in the context of autoimmune/inflammatory disease development (Tukaj and Węgrzyn 2016 ; Li et al 2020 ; Bregnhøj et al 2022 ; Tukaj and Sitko 2022 ; Ben Abdallah et al 2023 ). In fact, preclinical or clinical studies revealed that using Hsp90 inhibitors with N-terminal affinity seems to be promising for the treatment of non-infectious inflammatory skin diseases (Ben Abdallah et al 2023 ) including autoimmune bullous skin diseases or psoriasis due to attenuation of numerous inflammatory immune cells and signaling pathways (Kasperkiewicz et al 2011 ; Tukaj et al 2013 , 2014a , 2017 ; Li et al 2020 ; Bregnhøj et al 2022 ; Rittig et al 2023 ).…”