AUTHOR=Campione Elena , Mazzilli Sara , Di Prete Monia , Dattola Annunziata , Cosio Terenzio , Lettieri Barbato Daniele , Costanza Gaetana , Lanna Caterina , Manfreda Valeria , Gaeta Schumak Ruslana , Prignano Francesca , Coniglione Filadelfo , Ciprani Fabrizio , Aquilano Katia , Bianchi Luca 

TITLE=The Role of Glutathione-S Transferase in Psoriasis and Associated Comorbidities and the Effect of Dimethyl Fumarate in This Pathway

JOURNAL=Frontiers in Medicine

VOLUME=Volume 9 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2022.760852

DOI=10.3389/fmed.2022.760852

ISSN=2296-858X

ABSTRACT=Psoriasis vulgaris is a chronic inflammatory skin disease characterized by well-demarcated scaly plaques. Oxidative stress plays a crucial role in the psoriasis pathogenesis and is associated with the
disease severity. Dimethyl fumarate modulates pro-inflammatory transcription factors activity. This is responsible for the downregulation of inflammatory cytokines and an overall shift from a pro-
inflammatory to an anti-inflammatory/regulatory response. Both steps are necessary for the
amelioration of psoriatic inflammation, although additional mechanisms have been proposed. Several studies reported long term effectiveness and safety of dimethyl fumarate monotherapy in patient with moderate-to-severe psoriasis. Furthermore, psoriasis is a chronic disease associated often to metabolic comorbidities, as obesity, diabetes, and cardiovascular diseases, in which glutathione-S transferase deregulation is present. Glutathione-S transferase is involved in the antioxidant system. An increase of its activity in psoriatic epidermis in comparison with uninvolved and normal epidermal biopsies has been reported. Dimethyl fumarate depletes glutathione-S transferase by formation of covalently linked conjugates. This review investigates the anti-inflammatory role of dimethyl fumarate in oxidative stress and its effect by reducing oxidative stress. The glutathione-S transferase regulation is helpful in treating psoriasis, with anti-inflammatory effect on the keratinocytes hyperproliferation, and in modulation of metabolic comorbidities.