Crosstalk between NLRP3 signaling and histone deacetylases in inflammasome-driven diseases

The NLRP3 inflammasome is a validated therapeutic target in inflammatory, metabolic, and neurodegenerative diseases. Epigenetic regulators, particularly histone deacetylases (HDACs), have emerged as key modulators of inflammasome priming and activation. Recent advances in medicinal chemistry have pr...

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Detalles Bibliográficos
Autores: Tan, Kathrin, Rodríguez Fernández, María Mercedes, Keuler, Tim, Hansen, Finn K., Gütschow, Michael, Weindl, Günther, Marco-Contelles, José
Tipo de recurso: artículo
Fecha de publicación:2025
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/744320
Acceso en línea:https://hdl.handle.net/10486/744320
https://dx.doi.org/10.1021/acs.jmedchem.5c02657
Access Level:acceso embargado
Palabra clave:Neurodegenerative diseases
epigenetic regulators
histone deacetylases
inflammasomes
Química
Descripción
Sumario:The NLRP3 inflammasome is a validated therapeutic target in inflammatory, metabolic, and neurodegenerative diseases. Epigenetic regulators, particularly histone deacetylases (HDACs), have emerged as key modulators of inflammasome priming and activation. Recent advances in medicinal chemistry have provided new chemical modalities for the mechanistic interrogation and the potential therapeutic modulation of NLRP3 signaling. This Perspective dissects the mechanistic interface between HDAC-dependent epigenetic control and NLRP3 signaling and highlights emerging chemical tools, including isoform-selective inhibitors and targeted protein degraders. We discuss the challenges of isoform selectivity, species-specific differences, and the therapeutic potential of HDAC-based strategies to attenuate aberrant NLRP3 activity while minimizing off-target effects. Understanding this epigenetic-inflammasome crosstalk may provide a framework for translating epigenetic modulation into innovative treatments for inflammasome-driven diseases