Inhibition of neutrophilic serine proteases: a new direction of pathogenetic therapy in patients with psoriasis

Abstract

Psoriasis is a chronic inflammatory immune-mediated disease characterized by increased division rate and impaired differentiation of keratinocytes. Despite the rapid development and introduction of new systemic drugs, external therapy remains an integral part of the treatment of patients with psoriasis. A major disadvantage of this treatment is the low selectivity and the non-specificity of its anti-inflammatory action in various dermatoses, including psoriasis, which may manifest itself as adverse effects and insufficient therapeutic efficacy. This review presents a new direction in the treatment of psoriasis based on development of a drug that would inhibit serine proteases. Current information about mechanisms of psoriasis and the role of IL36-mediated inflammation is presented. Also, the review addresses serine proteases of the skin, specifically their endogenous and
synthetic low-molecular inhibitors. Prospects for implementation of this novel treatment, including results of preclinical studies, are described. Further development of this direction will allow improving the treatment of both limited and widespread forms of psoriasis, which may fundamentally change the approach to managing patients with this disease.