scholarly journals Growth Hormone Receptor Deficiency Protects against Age-Related NLRP3 Inflammasome Activation and Immune Senescence

Cell Reports ◽  
2016 ◽  
Vol 14 (7) ◽  
pp. 1571-1580 ◽  
Author(s):  
Olga Spadaro ◽  
Emily L. Goldberg ◽  
Christina D. Camell ◽  
Yun-Hee Youm ◽  
John J. Kopchick ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Nlrp3 Inflammasome ◽  
Hormone Receptor ◽  
Growth Hormone Receptor ◽  
Inflammasome Activation ◽  
Immune Senescence ◽  
Age Related ◽  
Nlrp3 Inflammasome Activation

Inhibition of NLRP3 inflammasome activation and pyroptosis with ethyl acetate fraction of Bungeanum ameliorated cognitive dysfunction in aged mice

2021 ◽  
Author(s):  
Meihuan Zhao ◽  
Yuan Dai ◽  
Ping Li ◽  
Jie wang ◽  
Tengyun Ma ◽  
...  
Keyword(s):  
Ethyl Acetate ◽  
Cognitive Dysfunction ◽  
Nlrp3 Inflammasome ◽  
Ethyl Acetate Fraction ◽  
Inflammasome Activation ◽  
Material Basis ◽  
Age Related ◽  
Nlrp3 Inflammasome Activation ◽  
Zanthoxylum Bungeanum ◽  
Zanthoxylum Bungeanum Maxim

Zanthoxylum bungeanum Maxim (Rutaceae), a homologous of medicine and foodstuff, has previously been demonstrated the potential prevention of age-related cognitive dysfunction. However, the mechanisms and material basis remain elusively understood....

scholarly journals Effects of Resvega on Inflammasome Activation in Conjunction with Dysfunctional Intracellular Clearance in Retinal Pigment Epithelial (RPE) Cells

Antioxidants ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 67
Author(s):  
Niina Bhattarai ◽  
Niina Piippo ◽  
Sofia Ranta-aho ◽  
Yashavanthi Mysore ◽  
Kai Kaarniranta ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Retinal Pigment ◽  
Membrane Integrity ◽  
Age Related Macular Degeneration ◽  
Inflammasome Activation ◽  
Rpe Cells ◽  
Caspase 1 ◽  
Protein Clearance ◽  
Age Related ◽  
Nlrp3 Inflammasome Activation

Age-related macular degeneration (AMD) is an eye disease in which retinal pigment epithelium (RPE) cells play a crucial role in maintaining retinal homeostasis and photoreceptors’ functionality. During disease progression, there is increased inflammation with nucleotide-binding domain, leucine-rich repeat, and Pyrin domain 3 (NLRP3) inflammasome activation, oxidative stress, and impaired autophagy in RPE cells. Previously, we have shown that the dietary supplement Resvega reduces reactive oxygen species (ROS) production and induces autophagy in RPE cells. Here, we investigated the ability of Resvega to prevent NLRP3 inflammasome activation with impaired protein clearance in human RPE cells. Cell viability was measured using the lactate dehydrogenase (LDH) and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Enzyme-linked immunosorbent assays (ELISA) were utilized to determine the secretion of cytokines, NLRP3, and vascular endothelial growth factor (VEGF). Caspase-1 activity was measured with a fluorescent labeled inhibitor of caspase-1 (FLICA; FAM-YVAD-FMK) and detected microscopically. Resvega improved the cell membrane integrity, which was evident as reduced LDH leakage from cells. In addition, the caspase-1 activity and NLRP3 release were reduced, as was the secretion of two inflammatory cytokines, interleukin (IL)-1β and IL-8, in IL-1α-primed ARPE-19 cells. According to our results, Resvega can potentially reduce NLRP3 inflammasome-mediated inflammation in RPE cells with impaired protein clearance.

scholarly journals Distinct effects of complement and of NLRP3- and non-NLRP3 inflammasomes for choroidal neovascularization

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Jakob Malsy ◽  
Andrea C Alvarado ◽  
Joseph O Lamontagne ◽  
Karin Strittmatter ◽  
Alexander G Marneros
Keyword(s):  
Choroidal Neovascularization ◽  
Nlrp3 Inflammasome ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Inflammasome Activation ◽  
Rpe Cells ◽  
Age Related ◽  
Nlrp3 Inflammasome Activation ◽  
Nlrp3 Inflammasomes

NLRP3 inflammasome activation and complement-mediated inflammation have been implicated in promoting choroidal neovascularization (CNV) in age-related macular degeneration (AMD), but central questions regarding their contributions to AMD pathogenesis remain unanswered. Key open questions are (1) whether NLRP3 inflammasome activation mainly in retinal pigment epithelium (RPE) or rather in non-RPE cells promotes CNV, (2) whether inflammasome activation in CNV occurs via NLRP3 or also through NLRP3-independent mechanisms, and (3) whether complement activation induces inflammasome activation in CNV. Here we show in a neovascular AMD mouse model that NLRP3 inflammasome activation in non-RPE cells but not in RPE cells promotes CNV. We demonstrate that both NLRP3-dependent and NLRP3-independent inflammasome activation mechanisms induce CNV. Finally, we find that complement and inflammasomes promote CNV through independent mechanisms. Our findings uncover an unexpected role of non-NLRP3 inflammasomes for CNV and suggest that combination therapies targeting inflammasomes and complement may offer synergistic benefits to inhibit CNV.

scholarly journals β-Hydroxybutyrate inhibits inflammasome activation to attenuate Alzheimer’s disease pathology

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Daniel C. Shippy ◽  
Connor Wilhelm ◽  
Patel A. Viharkumar ◽  
Thomas J. Raife ◽  
Tyler K. Ulland
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Nlrp3 Inflammasome ◽  
Ketone Bodies ◽  
Late Onset ◽  
Inflammasome Activation ◽  
Age Related ◽  
Nlrp3 Inflammasome Activation ◽  
5Xfad Mouse

Abstract Alzheimer’s disease (AD) is a progressive, late-onset dementia with no effective treatment available. Recent studies suggest that AD pathology is driven by age-related changes in metabolism. Alterations in metabolism, such as placing patients on a ketogenic diet, can alter cognition by an unknown mechanism. One of the ketone bodies produced as a result of ketogenesis, β-hydroxybutyrate (BHB), is known to inhibit NLRP3 inflammasome activation. Therefore, we tested if BHB inhibition of the NLRP3 inflammasome reduces overall AD pathology in the 5XFAD mouse model of AD. Here, we find BHB levels are lower in red blood cells and brain parenchyma of AD patients when compared with non-AD controls. Furthermore, exogenous BHB administration reduced plaque formation, microgliosis, apoptosis-associated speck-like protein containing a caspase recruitment domain (Asc) speck formation, and caspase-1 activation in the 5XFAD mouse model of AD. Taken together, our findings demonstrate that BHB reduces AD pathology by inhibiting NLRP3 inflammasome activation. Additionally, our data suggest dietary or pharmacological approaches to increase BHB levels as promising therapeutic strategies for AD.

scholarly journals Age-Related and Depot-Specific Changes in White Adipose Tissue of Growth Hormone Receptor-Null Mice

2013 ◽  
Vol 69 (1) ◽  
pp. 34-43 ◽  
Author(s):  
Lucila Sackmann-Sala ◽  
Darlene E. Berryman ◽  
Ellen R. Lubbers ◽  
Han Zhang ◽  
Clare B. Vesel ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Hormone Receptor ◽  
Growth Hormone Receptor ◽  
Age Related

scholarly journals TXNIP regulates age-associated neuroinflammation: Implication in Alzheimer’s disease

2020 ◽  
Author(s):  
Saifudeen Ismael ◽  
Sanaz Nasoohi ◽  
Arum Yoo ◽  
Lexiao Li ◽  
Khurram Aslam ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Nlrp3 Inflammasome ◽  
Experimental Studies ◽  
Inflammasome Activation ◽  
Control Analysis ◽  
Age Related ◽  
Nlrp3 Inflammasome Activation ◽  
Thioredoxin System

Abstract Background Immune system hypersensitivity with aging is believed to contribute to mental frailty in elderlies. This is postulated to arise from accumulation of oxidative molecular patterns. Solid evidences delineates thioredoxin interacting protein (TXNIP), an inducible protein involved in oxidative stress, is essential for NOD-like receptor pyrin domain containing-3 (NLRP3)-inflammasome activation which intimately connects “inflammaging” to senile cognitive decline. This study aims to fundamentally explore the plausible involvement of TXNIP/NLRP3 inflammasome pathway in senile dementia and the typical Alzhemier’s disease. Methods In experimental studies cerebral samples from gender-matched mice were compared for TXNIP/NLRP3 inflammasome activation and klotho depletion, through immunoblotting and immunostaining in different life span points. In aged males, genetic or pharmacological ablation of TXNIP were then used to determine effects on cognitive decline and sensorimotor frailty in morris water maze, novel object recognition test and gait control analysis. Immunoblotting/staining experiments were also performed on human postmortem aged hippocampal specimens and 5XFAD transgenic mice, to ultimately address Alzheimer’s disease (AD) as the most age related dementia. Results According to our preclinical studies, cerebral TXNIP was significantly upregulated in aged animals, paralleled by the NLRP3-inflammasome over-activity in both sexes, and closely associated klotho depletion in aged males. TXNIP knock-out reversed age-related NLRP3-hyperactivity and enhanced thioredoxin (TRX) levels in aged brains. Further, pharmacological TXNIP inhibition replicated the TXNIP/NLRP3-inflammasome downregulation in aged animals, with FOXO-1 and mTOR upregulation. These alterations concurred with substantial improvements in both cognitive and sensorimotor abilities. Moreover, our immunostaining shows a significant increase of TXNIP in transgenic 5XFAD mice brain and TXNIP/NLRP3-inflammasome activity in AD human postmortem hippocampal specimens, in proximity of p-tau tangles and β-amyloid plaques. Conclusion Together, these findings substantiate the pivotal role of TXNIP to drive inflammging in parallel with klotho depletion and functional decline. TXNIP co-localization with hallmarks of AD pathology is further supportive of potential mechanistic links between TXNIP and AD. Unraveling new information on upstream pathways, these data support modulating thioredoxin system as a potential approach to decelerate senile frailty.

Quercetin improves cognitive disorder in aging mice by inhibiting NLRP3 inflammasome activation

2021 ◽  
Author(s):  
Han Li ◽  
Fa-Jun Chen ◽  
Wei-Lin Yang ◽  
Han-Zi Qiao ◽  
Shi-Jie Zhang
Keyword(s):  
Neurodegenerative Diseases ◽  
Nlrp3 Inflammasome ◽  
Cognitive Disorder ◽  
Inflammasome Activation ◽  
Flavonoid Compounds ◽  
Age Related ◽  
Nlrp3 Inflammasome Activation ◽  
Dietary Flavonoid

Quercetin is one of the most abundant dietary flavonoid compounds, and its mechanism for combating age-related neurodegenerative diseases is unclear.

scholarly journals The Absence of NLRP3-inflammasome Modulates Hepatic Fibrosis Progression, Lipid Metabolism, and Inflammation in KO NLRP3 Mice during Aging

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2148
Author(s):  
Paloma Gallego ◽  
Beatriz Castejón-Vega ◽  
José A. del Campo ◽  
Mario D. Cordero
Keyword(s):  
Lipid Metabolism ◽  
Nlrp3 Inflammasome ◽  
Oxidative Stress Marker ◽  
Inflammasome Activation ◽  
Low Grade ◽  
Sod Activity ◽  
Protein Levels ◽  
Age Related ◽  
Nlrp3 Inflammasome Activation ◽  
Liver Changes

Aging is associated with metabolic changes and low-grade inflammation in several organs, which may be due to NLRP3 inflammasome activation. Methods: Here, we asked whether age-related liver changes such as lipid metabolism and fibrosis are reduced in aged mice lacking the NLRP3 inflammasome. We report reduced protein levels of lipid markers (MTP, FASN, DGAT1), SOD activity, oxidative stress marker PTPRG, and the fibrotic markers TPM2β, COL1-α1 associated with increased GATA4, in NLRP3 deficient mice. Fibrotic, lipid, and oxidative reduction in liver tissues of mice was more pronounced in those old KO NLRP3 mice than in the younger ones, despite their greater liver damage. These results suggest that absence of the NLRP3 inflammasome attenuates age-related liver fibrotic pathology in mice, suggesting that pharmacological targeting may be beneficial.

scholarly journals Long-Lived Growth Hormone Receptor Knockout Mice Show a Delay in Age-Related Changes of Body Composition and Bone Characteristics

2006 ◽  
Vol 61 (6) ◽  
pp. 562-567 ◽  
Author(s):  
M. S. Bonkowski ◽  
R. W. Pamenter ◽  
J. S. Rocha ◽  
M. M. Masternak ◽  
J. A. Panici ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Body Composition ◽  
Knockout Mice ◽  
Hormone Receptor ◽  
Growth Hormone Receptor ◽  
Age Related ◽  
Age Related Changes
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