New Insights on NLRP3 Inflammasome : Mechanisms of Activation, Inhibition, and Epigenetic Regulation

© 2024. The Author(s)..

Inflammasomes are important modulators of inflammation. Dysregulation of inflammasomes can enhance vulnerability to conditions such as neurodegenerative diseases, autoinflammatory diseases, and metabolic disorders. Among various inflammasomes, Nucleotide-binding oligomerization domain leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3) is the best-characterized inflammasome related to inflammatory and neurodegenerative diseases. NLRP3 is an intracellular sensor that recognizes pathogen-associated molecular patterns and damage-associated patterns resulting in the assembly and activation of NLRP3 inflammasome. The NLRP3 inflammasome includes sensor NLRP3, adaptor apoptosis-associated speck-like protein (ASC), and effector cysteine protease procaspase-1 that plays an imperative role in caspase-1 stimulation which further initiates a secondary inflammatory response. Regulation of NLRP3 inflammasome ameliorates NLRP3-mediated diseases. Much effort has been invested in studying the activation, and exploration of specific inhibitors and epigenetic mechanisms controlling NLRP3 inflammasome. This review gives an overview of the established NLRP3 inflammasome assembly, its brief molecular mechanistic activations as well as a current update on specific and non-specific NLRP3 inhibitors that could be used in NLRP3-mediated diseases. We also focused on the recently discovered epigenetic mechanisms mediated by DNA methylation, histone alterations, and microRNAs in regulating the activation and expression of NLRP3 inflammasome, which has resulted in a novel method of gaining insight into the mechanisms that modulate NLRP3 inflammasome activity and introducing potential therapeutic strategies for CNS disorders.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:19

Enthalten in:

Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology - 19(2024), 1 vom: 29. Feb., Seite 7

Sprache:

Englisch

Beteiligte Personen:

Kodi, Triveni [VerfasserIn]
Sankhe, Runali [VerfasserIn]
Gopinathan, Adarsh [VerfasserIn]
Nandakumar, Krishnadas [VerfasserIn]
Kishore, Anoop [VerfasserIn]

Links:

Volltext

Themen:

CNS disorders
DNA methylation
Epigenetic
Histone modifications
Inflammasomes
Journal Article
MicroRNAs
NLR Family, Pyrin Domain-Containing 3 Protein
NLRP3 inflammasome
Review

Anmerkungen:

Date Completed 01.03.2024

Date Revised 03.03.2024

published: Electronic

Citation Status MEDLINE

doi:

10.1007/s11481-024-10101-5

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM369114221