# Advances in the Molecular Pathogenesis and Targeted Therapy of Psoriasis: Molecular Pathogenesis of Psoriasis

## TL;DR

This paper reviews recent advances in understanding the molecular causes of psoriasis and the development of targeted therapies to treat it.

## Contribution

The paper highlights novel molecular mechanisms and emerging therapies, including new agents and multi-omics approaches for precision medicine.

## Key findings

- Single-cell RNA sequencing and transcriptomics have revealed key mechanisms like GSDME-mediated pyroptosis and IL-23/IL-17 axis activation.
- Targeted therapies such as IL-17 and IL-23 inhibitors show efficacy, but challenges like adverse events and treatment resistance remain.
- Biomarkers like calprotectin and miR-106a-5p offer potential for personalized treatment, though gaps in personalization persist.

## Abstract

Psoriasis, a chronic immune-mediated skin disorder affecting 2-3% of the global
population, is driven by a complex interplay of immune dysregulation,
keratinocyte dysfunction, and genetic/epigenetic alterations, with systemic
comorbidities like psoriatic arthritis and cardiovascular disease amplifying its
burden. Recent molecular insights, leveraging single-cell RNA sequencing and
transcriptomics, have elucidated key pathogenic mechanisms, including
GSDME-mediated pyroptosis, IL-23/IL-17 axis activation, YAP1-driven
proliferation, and epigenetic modulation via miR-106a-5p and lncRNA MEG3. These
findings have spurred targeted therapies: IL-17 inhibitors (e.g., secukinumab)
achieve rapid histologic remission, IL-23 inhibitors (e.g., risankizumab) offer
sustained efficacy, and novel approaches like hyperforin, Deu@Cal microneedles,
and concentrated growth factor (CGF) target diverse pathways in preclinical and
early clinical settings. However, challenges persist, including adverse events
(e.g., paradoxical eczema, MACEs), treatment resistance (81% biologic
switching), and gaps in personalization despite promising biomarkers (e.g.,
calprotectin, miR-106a-5p). Future directions emphasize multi-omics integration,
novel agents, and combination therapies to overcome these hurdles, aiming to
transform psoriasis management into a paradigm of precision medicine.