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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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
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spelling Crosstalk between NLRP3 signaling and histone deacetylases in inflammasome-driven diseasesTan, KathrinRodríguez Fernández, María MercedesKeuler, TimHansen, Finn K.Gütschow, MichaelWeindl, GüntherMarco-Contelles, JoséNeurodegenerative diseasesepigenetic regulatorshistone deacetylasesinflammasomesQuímicaThe 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 diseasesThe work of F.K.H., M.G., and G.W. is funded by the DFG GRK2873 (494832089). J.M.-C thanks AEI (Government of Spain) for support (Grants PID2019-105813RB-C21, PID2022-136530OB-I00, and RED2022-134511-T)Thieme GruppeFacultad de CienciasDepartamento de Química OrgánicaAgencia Estatal de Investigación20252025-12-23research articlehttp://purl.org/coar/resource_type/c_2df8fbb1AMhttp://purl.org/coar/version/c_ab4af688f83e57aainfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10486/744320https://dx.doi.org/10.1021/acs.jmedchem.5c0265741432240reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengembargoed accesshttp://purl.org/coar/access_right/c_f1cfinfo:eu-repo/semantics/embargoedAccessoai:repositorio.uam.es:10486/7443202026-06-23T12:46:27Z
dc.title.none.fl_str_mv Crosstalk between NLRP3 signaling and histone deacetylases in inflammasome-driven diseases
title Crosstalk between NLRP3 signaling and histone deacetylases in inflammasome-driven diseases
spellingShingle Crosstalk between NLRP3 signaling and histone deacetylases in inflammasome-driven diseases
Tan, Kathrin
Neurodegenerative diseases
epigenetic regulators
histone deacetylases
inflammasomes
Química
title_short Crosstalk between NLRP3 signaling and histone deacetylases in inflammasome-driven diseases
title_full Crosstalk between NLRP3 signaling and histone deacetylases in inflammasome-driven diseases
title_fullStr Crosstalk between NLRP3 signaling and histone deacetylases in inflammasome-driven diseases
title_full_unstemmed Crosstalk between NLRP3 signaling and histone deacetylases in inflammasome-driven diseases
title_sort Crosstalk between NLRP3 signaling and histone deacetylases in inflammasome-driven diseases
dc.creator.none.fl_str_mv Tan, Kathrin
Rodríguez Fernández, María Mercedes
Keuler, Tim
Hansen, Finn K.
Gütschow, Michael
Weindl, Günther
Marco-Contelles, José
author Tan, Kathrin
author_facet Tan, Kathrin
Rodríguez Fernández, María Mercedes
Keuler, Tim
Hansen, Finn K.
Gütschow, Michael
Weindl, Günther
Marco-Contelles, José
author_role author
author2 Rodríguez Fernández, María Mercedes
Keuler, Tim
Hansen, Finn K.
Gütschow, Michael
Weindl, Günther
Marco-Contelles, José
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Facultad de Ciencias
Departamento de Química Orgánica
Agencia Estatal de Investigación
dc.subject.none.fl_str_mv Neurodegenerative diseases
epigenetic regulators
histone deacetylases
inflammasomes
Química
topic Neurodegenerative diseases
epigenetic regulators
histone deacetylases
inflammasomes
Química
description 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
publishDate 2025
dc.date.none.fl_str_mv 2025
2025-12-23
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
AM
http://purl.org/coar/version/c_ab4af688f83e57aa
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/10486/744320
https://dx.doi.org/10.1021/acs.jmedchem.5c02657
41432240
url https://hdl.handle.net/10486/744320
https://dx.doi.org/10.1021/acs.jmedchem.5c02657
identifier_str_mv 41432240
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv embargoed access
http://purl.org/coar/access_right/c_f1cf
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/embargoedAccess
rights_invalid_str_mv embargoed access
http://purl.org/coar/access_right/c_f1cf
eu_rights_str_mv embargoedAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Thieme Gruppe
publisher.none.fl_str_mv Thieme Gruppe
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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