Targeting toll-like receptor 4 (TLR4) and the NLRP3 inflammasome: Novel and emerging therapeutic targets for hyperuricaemia nephropathy.

Content Provider	Europe PMC
Author	Zhang, Chao Yang, Yanlang
Copyright Year	2024
Abstract	The clinical manifestation of hyperuricaemia, known as hyperuricaemia nephropathy, is relatively common. Its pathophysiology is largely based on chronic inflammation in circulatory and renal tissues. Toll-like receptor 4 (TLR4), a subclass of innate immune receptors, detects both pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), initiating inflammatory and immune responses that lead to the release of pro-inflammatory cytokines interleukin 1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α). These cytokines are pivotal in renal inflammation, especially in conditions like hyperuricaemia, acute renal injury, ischemia-reperfusion injury, and acute renal failure. The nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain-containing 3 (NLRP3) inflammasome, an essential component of the innate immune signaling complex, plays a central role in inflammation. It finely regulates the activation of caspase-1 and the production and secretion of the pro-inflammatory cytokine IL-1β, mediating and amplifying the inflammatory cascade response. Activation of TLR4 indirectly promotes the assembly of the NLRP3 inflammasome by regulating the nuclear factor kappa B (NF-κB) signaling pathway, thereby amplifying the inflammatory process and playing a significant pro-inflammatory role in hyperuricaemia nephropathy. TLR4 and NLRP3 inflammasome are anticipated to be novel markers and therapeutic targets for assessing treatment efficacy and prognosis in hyperuricaemia nephropathy. This paper provides a comprehensive overview of the structural composition and biological functions of TLR4 and NLRP3 inflammasome and systematically reviews their relevance in the pathogenesis of hyperuricaemia nephropathy.
Related Links	https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC11293219&blobtype=pdf
ISSN	28310896
Volume Number	24
DOI	10.17305/bb.2023.9838
PubMed Central reference number	PMC11293219
Issue Number	4
PubMed reference number	38041694
Journal	Biomolecules and Biomedicine [Biomol Biomed]
e-ISSN	2831090X
Language	English
Publisher	Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina
Publisher Date	2023-12-01
Access Restriction	Open
Rights License	This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/). © 2023 Zhang and Yang.
Subject Keyword	Hyperuricaemia nephropathy pathogenesis inflammation toll-like receptor 4 (TLR4) nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain-containing 3 (NLRP3)
Content Type	Text
Resource Type	Article
Subject	Biochemistry, Genetics and Molecular Biology