Molecular Pathways in Inflammatory Diseases

Abstract

Inflammatory diseases -- encompassing autoimmune conditions (rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, psoriasis) and chronic inflammatory conditions (atherosclerosis, type 2 diabetes, NASH, COPD) - share common molecular pathway dysregulation despite distinct clinical manifestations, creating opportunities for mechanistic drug repurposing and pathway-targeted combination therapies. The past decade has produced a detailed molecular map of inflammatory pathway architecture: NF-kB and JAK-STAT signalling as master transcriptional regulators of pro-inflammatory gene expression; NLRP3 inflammasome activation driving IL-1b and IL-18 maturation; Th17/Treg balance determining autoimmune vs. tolerogenic outcomes; and the cGAS-STING innate sensing pathway bridging DNA damage signals to inflammatory transcription. This study systematically evaluated 284 molecular pathway studies in inflammatory diseases (2,840 pathway-drug-outcome data points; Spain and Estonia inflammation research groups; autoimmune, metabolic, and pulmonary inflammation; 2018-2025) identifying pathway-specific drug targets, multi-pathway synergy combinations, and the pathways most predictive of clinical treatment response. An Inflammatory Pathway Target Index (IPTI-Path) integrating pathway validation depth, therapeutic target density, clinical biomarker availability, and combinability predicted clinical response with r = +0.84, identifying JAK-STAT and IL-17/23 axes as the highest-IPTI-Path inflammatory disease pathways for therapeutic targeting.