Inhibiting the NLRP3 Inflammasome

El-Sharkawy, Lina Y; Brough, David; Freeman, Sally

doi:10.3390/molecules25235533

Cited by 80 publications

(72 citation statements)

References 46 publications

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“…The NLRP3 inflammasome significantly contributes to neuroinflammation and age-related cognitive decline and is potently activated by Aβ [ 381 ]. Novel specific inhibitors of the NLRP3 inflammasome are currently in pre-clinical or clinical trials [ 382 ] (ifmthera.com/pipeline). MCC950 (also known as CP-456,773 and CRID-3), a potent inhibitor of NLRP3, promotes microglial clearance of Aβ, reduces Aβ accumulation, and improves cognitive function in APP/PS1 mice [ 383 , 384 , 385 , 386 ].…”

Section: Possible Intervention For Neuroinflammation In Admentioning

confidence: 99%

Neuroinflammation in Alzheimer’s Disease

et al. 2021

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Alzheimer’s disease (AD) is a neurodegenerative disease associated with human aging. Ten percent of individuals over 65 years have AD and its prevalence continues to rise with increasing age. There are currently no effective disease modifying treatments for AD, resulting in increasingly large socioeconomic and personal costs. Increasing age is associated with an increase in low-grade chronic inflammation (inflammaging) that may contribute to the neurodegenerative process in AD. Although the exact mechanisms remain unclear, aberrant elevation of reactive oxygen and nitrogen species (RONS) levels from several endogenous and exogenous processes in the brain may not only affect cell signaling, but also trigger cellular senescence, inflammation, and pyroptosis. Moreover, a compromised immune privilege of the brain that allows the infiltration of peripheral immune cells and infectious agents may play a role. Additionally, meta-inflammation as well as gut microbiota dysbiosis may drive the neuroinflammatory process. Considering that inflammatory/immune pathways are dysregulated in parallel with cognitive dysfunction in AD, elucidating the relationship between the central nervous system and the immune system may facilitate the development of a safe and effective therapy for AD. We discuss some current ideas on processes in inflammaging that appear to drive the neurodegenerative process in AD and summarize details on a few immunomodulatory strategies being developed to selectively target the detrimental aspects of neuroinflammation without affecting defense mechanisms against pathogens and tissue damage.

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Section: Possible Intervention For Neuroinflammation In Admentioning

confidence: 99%

Neuroinflammation in Alzheimer’s Disease

et al. 2021

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“…The NLRP3 inflammasome consists of the protein NLRP3 complexed with the proteins ASC and caspase-1, along with several accessory proteins, including NEK7 [ 39 ]. Formation of NLRP3 inflammasomes typically requires a priming step, in which the activated transcription factor Nuclear factor kappa beta (NF-kappaB) drives increased expression of NLRP3 and of pro-interleukin-1β and -18.…”

Section: Mechanisms Involved In the Priming And Activation Of Inflmentioning

confidence: 99%

Nutraceutical Strategies for Suppressing NLRP3 Inflammasome Activation: Pertinence to the Management of COVID-19 and Beyond

et al. 2020

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Inflammasomes are intracellular protein complexes that form in response to a variety of stress signals and that serve to catalyze the proteolytic conversion of pro-interleukin-1β and pro-interleukin-18 to active interleukin-1β and interleukin-18, central mediators of the inflammatory response; inflammasomes can also promote a type of cell death known as pyroptosis. The NLRP3 inflammasome has received the most study and plays an important pathogenic role in a vast range of pathologies associated with inflammation—including atherosclerosis, myocardial infarction, the complications of diabetes, neurological and autoimmune disorders, dry macular degeneration, gout, and the cytokine storm phase of COVID-19. A consideration of the molecular biology underlying inflammasome priming and activation enables the prediction that a range of nutraceuticals may have clinical potential for suppressing inflammasome activity—antioxidants including phycocyanobilin, phase 2 inducers, melatonin, and N-acetylcysteine, the AMPK activator berberine, glucosamine, zinc, and various nutraceuticals that support generation of hydrogen sulfide. Complex nutraceuticals or functional foods featuring a number of these agents may find utility in the prevention and control of a wide range of medical disorders.

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“…In these models, TET2 -deficient macrophages showed upregulation of several inflammatory cytokines part of the NLRP3 inflammasome complex, which is known to contribute to both atherogenesis and MDS pathogenesis [ 67 ]. In particular, it has been shown that interleukin-1β upregulates the expression of P-selectin in endothelial cells, a known chemo-attracting agent for monocytes, currently evaluated as a possible actionable target in the setting of CHIP and MDS to decrease cardiovascular risk [ 68 , 69 ]. Another approach currently in evaluation is the use of vitamin C, taking into account the recent data on its role in restoring some TET2 functions [ 70 , 71 ].…”

Section: Clinical Implications Of Chip: a Focus On Cardiovascular mentioning

confidence: 99%

From Clonal Hematopoiesis to Therapy-Related Myeloid Neoplasms: The Silent Way of Cancer Progression

Gurnari

Fabiani

Falconi

et al. 2021

Biology

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Clonal hematopoiesis (CH) has been recognized as a predisposing factor for the development of myeloid malignancies. Its detection has been reported at different frequencies across studies, based on the type of genome scanning approach used and the population studied, but the latest insights recognize its virtual ubiquitous presence in older individuals. The discovery of CH in recent years paved the way for a shift in the paradigm of our understanding of the biology of therapy-related myeloid malignancies (t-MNs). Indeed, we moved from the concept of a treatment-induced lesion to a model where CH precedes the commencement of any cancer-related treatment in patients who subsequently develop a t-MN. Invariant patterns of genes seem to contribute to the arising of t-MN cases, with differences regarding the type of treatment received. Here, we review the principal studies concerning CH, the relationship with myeloid progression and the mechanisms of secondary t-MN development.

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Inhibiting the NLRP3 Inflammasome

Cited by 80 publications

References 46 publications

Neuroinflammation in Alzheimer’s Disease

Neuroinflammation in Alzheimer’s Disease

Nutraceutical Strategies for Suppressing NLRP3 Inflammasome Activation: Pertinence to the Management of COVID-19 and Beyond

From Clonal Hematopoiesis to Therapy-Related Myeloid Neoplasms: The Silent Way of Cancer Progression

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