Portraying molecular modulation and therapeutic aspects of psoriasis: Retrospection and current status

Abstract

• Psoriasis is an autoimmune disease of the skin with chronic inflammatory conditions. • Various signaling pathways are involved in its pathophysiology. • The basis of molecular modulation of psoriasis has been addressed. • Various strategies to counter this complex disease have been discussed in detail. • Recent development in the anti-psoriatic therapy has been discussed. Psoriasis is a hyperproliferative skin disorder which is associated with dysregulation of the immune system. In this genetically transmitted disease, the immune system is activated by various triggers such as genetic predisposition, stress, and pathogenic microbes which in turn stimulate various immunocytes such as keratinocytes, macrophages, monocytes, dendritic cells and T-cells to secrete various pro-inflammatory cytokines that ultimately accelerate inflammation and cause psoriatic plaques. These cytokines are also responsible for T-cell differentiation, keratinocyte hyperproliferation, and accumulation of neutrophils and lymphocytes in the skin. At the molecular level, several pathways have been proposed underlying the pathophysiology of psoriasis that directly or indirectly kindle various psoriatic factors. The most common pathways include PDE-4, ICAM-1, LFA-1 and JAK/STAT pathways. In order to target these pathways, various strategies have been developed that counter moderate to severe psoriasis. The most effective therapies include interleukin inhibitors, TNF-α inhibitors, JAK inhibitors, PDE-4 inhibitors and immunosuppressants such as methotrexate, cyclosporin, tazarotene, and acitretin. Apart from these inhibitors, phototherapy (UV-A and PUVA) and topical therapies (corticosteroids, vitamin D analogs, retinoids, emollients, and keratolytic agents) have also been employed for the treatment of mild to moderate psoriasis. This review provides the retrospective analysis of psoriasis and current therapeutic options which are under development for the amelioration of psoriatic diseases. The information provided in this report may be helpful for the research community engaged in the development of effective novel therapies against psoriasis.