Mechanisms of NLRP3 activation and pathology during neurodegeneration

Jose, Sara; Groves, Natalie J.; Roper, Kathrein E.; Gordon, Richard D.

doi:10.1016/j.biocel.2022.106273

Cited by 13 publications

(8 citation statements)

References 102 publications

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“…JC-124 blocks the expression of NLRP3, ASC, Caspase 1 and pro-IL-1b, but its molecular mechanism are still under investigation (Marchetti et al, 2015). that the pharmacological inhibition of the NLRP3 inflammasome pathway has for example, a neuroprotective role in different disease models, therefore providing convincing arguments to further evaluate the potential of targeting the NLRP3 inflammasome (Jose et al, 2022).…”

Section: Inflammasome Disorders and Its Implications In Human Diseasesmentioning

confidence: 99%

“…In addition, the NLRP3 structure and activation mechanisms are still poorly understood which has delayed the development of novel therapeutics. Nevertheless, there are pre‐clinical evidences that the pharmacological inhibition of the NLRP3 inflammasome pathway has for example, a neuroprotective role in different disease models, therefore providing convincing arguments to further evaluate the potential of targeting the NLRP3 inflammasome (Jose et al., 2022 ).…”

Section: Inflammasome Disorders and Its Implications In Human Diseasesmentioning

confidence: 99%

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The inflammasome in biomaterial‐driven immunomodulation

Vasconcelos

Águas

Barbosa

2022

J Tissue Eng Regen Med

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Inflammasomes are intracellular structures formed upon the assembly of several proteins that have a considerable size and are very important in innate immune responses being key players in host defense. They are assembled after the perception of pathogens or danger signals. The activation of the inflammasome pathway induces the production of high levels of the pro‐inflammatory cytokines Interleukin (IL)‐1β and IL‐18 through the caspase activation. The procedure for the implantation of a biomaterial causes tissue injury, and the injured cells will secrete danger signals recognized by the inflammasome. There is growing evidence that the inflammasome participates in a number of inflammatory processes, including pathogen clearance, chronic inflammation and tissue repair. Therefore, the control of the inflammasome activity is a promising target in the development of capable approaches to be applied in regenerative medicine. In this review, we revisit current knowledge of the inflammasome in the inflammatory response to biomaterials and point to the yet underexplored potential of the inflammasome in the context of immunomodulation.

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Section: Inflammasome Disorders and Its Implications In Human Diseasesmentioning

confidence: 99%

Section: Inflammasome Disorders and Its Implications In Human Diseasesmentioning

confidence: 99%

The inflammasome in biomaterial‐driven immunomodulation

Vasconcelos

Águas

Barbosa

2022

J Tissue Eng Regen Med

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“…Immune cells recognize the damage-associated molecular patterns (DAMPs) through receptors called pattern recognition receptors (PRRs). For the neurodegenerative diseases, the recognition of DAMPs via amyloid beta (Aβ) in AD, alpha-synuclein in PD, the mutant superoxide dismutase-1 (SOD-1) gene or transactive response DNA binding protein 43 (TDP-43) in amyotrophic lateral sclerosis (ALS) by PRRs leads to the activation of the resident brain immune cells such as microglia, resulting in neuroinflammation and neurodegenerative disease development and progression [ 33 ]. A recent study indicated that Aβ activates NLRP3 inflammasome via Toll-like receptor-4 in mouse microglia, resulting in the release of mature IL-1β [ 34 ]; additionally, aggregated Aβ also results in increasing phagocytosis and cytokine production and the promotion of neuroinflammation, consequently causing synapse loss and neurodegeneration [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Nordalbergin Exerts Anti-Neuroinflammatory Effects by Attenuating MAPK Signaling Pathway, NLRP3 Inflammasome Activation and ROS Production in LPS-Stimulated BV2 Microglia

Liu

et al. 2023

IJMS

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Microglia-associated neuroinflammation is recognized as a critical factor in the pathogenesis of neurodegenerative diseases; however, there is no effective treatment for the blockage of neurodegenerative disease progression. In this study, the effect of nordalbergin, a coumarin isolated from the wood bark of Dalbergia sissoo, on lipopolysaccharide (LPS)-induced inflammatory responses was investigated using murine microglial BV2 cells. Cell viability was assessed using the MTT assay, whereas nitric oxide (NO) production was analyzed using the Griess reagent. Secretion of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) was detected by the ELISA. The expression of inducible NO synthase (iNOS), cyclooxygenase (COX)-2, mitogen-activated protein kinases (MAPKs) and NLRP3 inflammasome-related proteins was assessed by Western blot. The production of mitochondrial reactive oxygen species (ROS) and intracellular ROS was detected using flow cytometry. Our experimental results indicated that nordalbergin ≤20 µM suppressed NO, IL-6, TNF-α and IL-1β production; decreased iNOS and COX-2 expression; inhibited MAPKs activation; attenuated NLRP3 inflammasome activation; and reduced both intracellular and mitochondrial ROS production by LPS-stimulated BV2 cells in a dose-dependent manner. These results demonstrate that nordalbergin exhibits anti-inflammatory and anti-oxidative activities through inhibiting MAPK signaling pathway, NLRP3 inflammasome activation and ROS production, suggesting that nordalbergin might have the potential to inhibit neurodegenerative disease progression.

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“…The NLRP3 inflammasome has been found activated by many different stimuli, such as the increased extracellular glucose level in a diabetic setting ( 26 ). However, the exact molecular regulation of NLRP3 activation appeared to be complex and controlled by multiple factors ( 27 , 28 ). It has been reported that NLRP3 is activated in different types of diabetes, while NLRP3 depletion seemed to have a protective effect against diabetes ( 29 , 30 ).…”

Section: Discussionmentioning

confidence: 99%

NLRP3+ macrophages aggravate inflammatory cystitis in diabetes

Peng

Gao

2022

Front. Immunol.

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Inflammatory macrophages play a pivotal role in the progression of inflammatory cystitis. Formation of NOD-, LRR- and PYD domains-containing protein 3 (NLRP3) inflammasome triggers the activation of caspase-1/IL-1β signaling cascades to mediate inflammatory response. However, it is not known whether NLRP3 activation in macrophages during cystitis may differ in normal or diabetic setting as well as the importance of it. In this study, we found that NLRP3 levels significantly increased in bladder macrophages in diabetic mice that underwent cystitis. Moreover, bladder macrophages from diabetic mice appeared to have increased their potential of growth, migration and phagocytosis. Furthermore, specific depletion of NLRP3 in macrophages alleviated the severity of cystitis in diabetic mice, but not in non-diabetic mice. Together, our data suggest that NLRP3 depletion in macrophages may be a promising strategy for treating diabetic cystitis.

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Mechanisms of NLRP3 activation and pathology during neurodegeneration

Cited by 13 publications

References 102 publications

The inflammasome in biomaterial‐driven immunomodulation

The inflammasome in biomaterial‐driven immunomodulation

Nordalbergin Exerts Anti-Neuroinflammatory Effects by Attenuating MAPK Signaling Pathway, NLRP3 Inflammasome Activation and ROS Production in LPS-Stimulated BV2 Microglia

NLRP3+ macrophages aggravate inflammatory cystitis in diabetes

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