The role of NLRP3 and NLRP12 inflammasomes in glioblastoma.

Autor: Rajkhowa S; Department of Bioscience and Bioengineering, Indian Institute of Technology Jodhpur, Jodhpur, Rajasthan, India., Jha S; Department of Bioscience and Bioengineering, Indian Institute of Technology Jodhpur, Jodhpur, Rajasthan, India. sushmitajha@iitj.ac.in.
Jazyk: angličtina
Zdroj: Genes and immunity [Genes Immun] 2024 Nov 27. Date of Electronic Publication: 2024 Nov 27.
DOI: 10.1038/s41435-024-00309-z
Abstrakt: Glioblastoma (GBM) is the deadliest malignant brain tumor, with a survival of less than 14 months after diagnosis. The highly invasive nature of GBM makes total surgical resection challenging, leading to tumor recurrence and declined survival. The heterocellular composition of the GBM reprograms its microenvironment, favoring tumor growth, proliferation, and migration. The innate immune cells in the GBM tumor microenvironment, including microglia, astrocytes, and macrophages, express pattern recognition receptors such as NLRs (Nucleotide-binding domain and leucine-rich repeat-containing) that sense pathogen- and damage-associated molecular patterns initiating inflammation. Upon activation, NLRP3 promotes inflammation by NLRP3 inflammasome formation. Auto-proteolytic cleavage and activation of Caspase-1 within the inflammasome leads to caspase-1-mediated cleavage, activation, and conversion of pro-IL-1ß and pro-IL-18 to IL-1ß and IL-18, leading to pyroptosis. In contrast, NLRP12 downregulates inflammatory responses in microglia and macrophages by regulating the NF-κB pathway. NLRP3 and NLRP12 have been implicated in the disease pathophysiology of several cancers with cell-context-dependent, pro- or anti-tumorigenic roles. In this review, we discuss the current literature on the mechanistic roles of NLRP3 and NLRP12 in GBM and the gaps in the scientific literature in the context of GBM pathophysiology with potential for targeted therapeutics.
Competing Interests: Competing interests: The authors declare no competing interests.
(© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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