Navigating the landscape of psoriasis therapy: novel targeted pathways and emerging trends

ABSTRACT

Introduction

Psoriasis is a chronic, inflammatory, non-communicable skin disorder that affects a patient’s social and emotional well-being. It is characterized by hyperproliferation of keratinocytes, irregular shedding of skin cells, and abnormal invasion of inflammatory mediators. The treatment strategy is designed based on the severity of the disease condition starting from topical, phototherapy, systemic, and biologics. In recent years, extensive research into the underlying mechanisms of psoriasis has led to significant advancement in treatment options from small molecules to biologics.

Area covered

This review focuses on intracellular and molecular mechanisms such as AhR, A3AR, RIP1, CGRP, and S1P that serve as novel pharmacological targets for psoriasis. Moreover, new molecules are approved or are under clinical investigation to interfere with these target mechanisms.

Expert opinion

A detailed understanding of signaling pathways provides potential targets and molecular mechanisms for the inflammatory cascade in psoriasis. This has led to the development of small molecules targeting specific pathways. Further, the combination of nanotechnology can assist in dose reduction leading to reduced adverse effects in the management of psoriasis.

KEYWORDS:

• Adenosine A3 receptor
• molecular targets
• aryl hydrogen receptor pathway (AhR)
• psoriasis
• sphingosine 1 phosphate (S1P)

Article highlights

• Psoriasis is a chronic autoimmune skin disorder affecting 2-3% of the world population.

• Identification and understanding of various intracellular signaling pathways and endogenous molecules hold substantial importance.

• Novel pharmacological targets recognized for the management of psoriasis.

• The targets include AhR, CGRP, RIP-1 kinase, A3AR, BRD-BET and S1P.

• The novel agonist and antagonist molecules that bind to these pharmacological targets have been compiled.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

The authors gratefully acknowledge the Department of Health Research, ICMR, Govt of India (Proposal ID: GIA/2020/000353).

Additional information

Funding

This paper was not funded.