Exploring the role of EZH2 in neuroinflammation: implications for innovative therapeutic strategies

The central nervous system (CNS) disease hallmark, neuroinflammation, is regulated by EZH2, an essential epigenetic regulator that controls CNS immune signaling and inflammatory pathways. The research demonstrates that EZH2 inhibitors regulate neuroinflammation by affecting microglial activation, cytokine production, and non-coding RNA (ncRNA) networks. The preclinical studies demonstrate encouraging results; however, researchers need to overcome three major obstacles: off-target effects, drug resistance, and issues related to blood-brain barrier (BBB) permeability. The review elucidates EZH2-targeting methods, as well as their combination with conventional anti-inflammatory therapies, novel drug delivery systems, and BBB penetration enhancers, aiming to improve CNS delivery and enhance both specificity and efficacy. The review presents innovative EZH2-based therapeutic approaches for neuroinflammatory diseases, based on an analysis of existing data and the identification of key knowledge gaps.