The Role of Melatonin on NLRP3 Inflammasome Activation in Diseases

Arioz, Burak I.; Tarakcioglu, Emre; Olcum, Melis; Genç, Şermin

doi:10.3390/antiox10071020

Cited by 31 publications

(27 citation statements)

References 175 publications

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“…Heightened expression of the NLRP3 inflammasome was detected in leukocytes in the lungs of all patients who did not survive COVID-19 [ 491 ]. Melatonin targets NLRP3 inflammasome-mediated cytokine release employing antioxidant-dependent and -independent mechanisms [ 492 ].…”

Section: Melatonin Protects Mitochondria and Atp Production To Inhibi...mentioning

confidence: 99%

Melatonin: Regulation of Viral Phase Separation and Epitranscriptomics in Post-Acute Sequelae of COVID-19

Loh¹,

Reíter

2022

IJMS

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The relentless, protracted evolution of the SARS-CoV-2 virus imposes tremendous pressure on herd immunity and demands versatile adaptations by the human host genome to counter transcriptomic and epitranscriptomic alterations associated with a wide range of short- and long-term manifestations during acute infection and post-acute recovery, respectively. To promote viral replication during active infection and viral persistence, the SARS-CoV-2 envelope protein regulates host cell microenvironment including pH and ion concentrations to maintain a high oxidative environment that supports template switching, causing extensive mitochondrial damage and activation of pro-inflammatory cytokine signaling cascades. Oxidative stress and mitochondrial distress induce dynamic changes to both the host and viral RNA m6A methylome, and can trigger the derepression of long interspersed nuclear element 1 (LINE1), resulting in global hypomethylation, epigenetic changes, and genomic instability. The timely application of melatonin during early infection enhances host innate antiviral immune responses by preventing the formation of “viral factories” by nucleocapsid liquid-liquid phase separation that effectively blockades viral genome transcription and packaging, the disassembly of stress granules, and the sequestration of DEAD-box RNA helicases, including DDX3X, vital to immune signaling. Melatonin prevents membrane depolarization and protects cristae morphology to suppress glycolysis via antioxidant-dependent and -independent mechanisms. By restraining the derepression of LINE1 via multifaceted strategies, and maintaining the balance in m6A RNA modifications, melatonin could be the quintessential ancient molecule that significantly influences the outcome of the constant struggle between virus and host to gain transcriptomic and epitranscriptomic dominance over the host genome during acute infection and PASC.

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Section: Melatonin Protects Mitochondria and Atp Production To Inhibi...mentioning

confidence: 99%

Melatonin: Regulation of Viral Phase Separation and Epitranscriptomics in Post-Acute Sequelae of COVID-19

Loh¹,

Reíter

2022

IJMS

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“…It has been found that many natural and endogenous or exogenous molecules exert anti-inflammatory effects by inhibiting NLRP3 inflammasome activation in OP. Arioz ect (70). have summarized the effect of melatonin, a widely used natural and endogenous molecule, on NLRP3 in a variety of different diseases.…”

Section: Potential Therapeutic Target Of Nlrp3 Inflammasome In Opmentioning

confidence: 99%

NLRP3 Inflammasome: A New Target for Prevention and Control of Osteoporosis?

Jiang

Yang

et al. 2021

Front. Endocrinol.

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Osteoporosis is a systemic bone metabolism disease that often causes complications, such as fractures, and increases the risk of death. The nucleotide-binding oligomerization domain-like-receptor family pyrin domain-containing 3 (NLRP3) inflammasome is an intracellular multiprotein complex that regulates the maturation and secretion of Caspase-1 dependent proinflammatory cytokines interleukin (IL)-1β and IL-18, mediates inflammation, and induces pyroptosis. The chronic inflammatory microenvironment induced by aging or estrogen deficiency activates the NLRP3 inflammasome, promotes inflammatory factor production, and enhances the inflammatory response. We summarize the related research and demonstrate that the NLRP3 inflammasome plays a vital role in the pathogenesis of osteoporosis by affecting the differentiation of osteoblasts and osteoclasts. IL-1β and IL-18 can accelerate osteoclast differentiation by expanding inflammatory response, and can also inhibit the expression of osteogenic related proteins or transcription factors. In vivo and in vitro experiments showed that the overexpression of NLRP3 protein was closely related to aggravated bone resorption and osteogenesis deficiency. In addition, abnormal activation of NLRP3 inflammasome can not only produce inflammation, but also lead to pyroptosis and dysfunction of osteoblasts by upregulating the expression of Caspase-1 and gasdermin D (GSDMD). In conclusion, NLRP3 inflammasome overall not only accelerates bone resorption, but also inhibits bone formation, thus increasing the risk of osteoporosis. Thus, this review highlights the recent studies on the function of NLRP3 inflammasome in osteoporosis, provides information on new strategies for managing osteoporosis, and investigates the ideal therapeutic target to treat osteoporosis.

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“…The NLRP3 inflammasome is a cytosolic multiprotein comprised of the NOD-like receptor, and adaptor and effector proteins that trigger the release of specific cytokines (e.g., IL-1β and IL-18) and initiate the innate immune system cascade, having an established role in the pathogenesis of numerous inflammatory conditions. As such, the inhibition of the NLRP3 inflammasome by melatonin as a result of its anti-inflammatory properties, could advance treatment options for a range of inflammatory conditions [15,16].…”

mentioning

confidence: 99%

“…In such a context, Arioz et al summarised the in vitro and in vivo studies that assessed this effect of melatonin on NLRP3 inflammasome-associated conditions [15]. It was concluded that melatonin can inhibit NLRP3 by regulating non-coding RNAs and has an overall anti-inflammatory effect with the inhibition of inflammatory pathways, such as NFκB, and the activation of mitophagy and the Nrf2/NFE2L2 pathway, diminishing ROS generation.…”

mentioning

confidence: 99%