Interplay Between NLRP3 Inflammasome and Autophagy

Frontiers in Immunology, Год журнала: 2020, Номер 11

Опубликована: Окт. 9, 2020

The NLRP3 inflammasome is cytosolic multi-protein complex that induces inflammation and pyroptotic cell death in response to both pathogen (PAMPs) endogenous activators (DAMPs). Recognition of PAMPs or DAMPs leads formation the complex, which results activation caspase-1, followed by cleavage release pro-inflammatory cytokines. Excessive can contribute development inflammatory diseases cancer. Autophagy vital intracellular process for recycling removal damaged proteins organelles, as well destruction pathogens. Cytosolic components are sequestered a double-membrane vesicle – autophagosome, then fuses with lysosome resulting degradation cargo. autophagy dysfunction lead hyperinflammation excessive thus acts major regulator inflammasomes. Autophagic activators, such DAMPs, cytokines reduce response. Likewise, signaling pathways regulate autophagic necessary balance between required host defense prevention detrimental inflammation. has protective role some associated inflammasome, including gouty arthritis, familial Mediterranean fever sepsis. Understanding interregulation these two essential biological processes comprehend mechanisms designing possible treatments multiple

Язык: Английский

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NAD+ improves cognitive function and reduces neuroinflammation by ameliorating mitochondrial damage and decreasing ROS production in chronic cerebral hypoperfusion models through Sirt1/PGC-1α pathway

Journal of Neuroinflammation, Год журнала: 2021, Номер 18(1)

Опубликована: Сен. 16, 2021

Microglial-mediated neuroinflammation plays an important role in vascular dementia, and modulating has emerged as a promising treatment target. Nicotinamide adenine dinucleotide (NAD

Язык: Английский

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Targeting microglial autophagic degradation in NLRP3 inflammasome-mediated neurodegenerative diseases

Ageing Research Reviews, Год журнала: 2020, Номер 65, С. 101202 - 101202

Опубликована: Ноя. 5, 2020

Язык: Английский

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Alzheimer’s Disease Pathogenesis: Role of Autophagy and Mitophagy Focusing in Microglia

International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(7), С. 3330 - 3330

Опубликована: Март 24, 2021

Alzheimer's disease (AD) is a debilitating neurological disorder, and currently, there no cure for it. Several pathologic alterations have been described in the brain of AD patients, but ultimate causative mechanisms are still elusive. The classic hallmarks AD, including amyloid plaques (Aβ) tau tangles (tau), most studied features AD. Unfortunately, all efforts targeting these pathologies failed to show desired efficacy patients so far. Neuroinflammation impaired autophagy two other main known It has reported that exist long before emergence any clinical manifestation Microglia inflammatory cells considered by many researchers as next hope finding viable therapeutic target Interestingly, it appears mitophagy also changed Inside cells, inflammation interact bidirectional manner. In current review, we briefly discussed an overview on then provided comprehensive discussion role pathways microglia their involvement pathogenesis.

Язык: Английский

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The role of inflammasomes in vascular cognitive impairment

Molecular Neurodegeneration, Год журнала: 2022, Номер 17(1)

Опубликована: Янв. 9, 2022

There is an increasing prevalence of Vascular Cognitive Impairment (VCI) worldwide, and several studies have suggested that Chronic Cerebral Hypoperfusion (CCH) plays a critical role in disease onset progression. However, there limited understanding the underlying pathophysiology VCI, especially relation to CCH. Neuroinflammation significant contributor progression VCI as increased systemic levels proinflammatory cytokine interleukin-1β (IL-1β) has been extensively reported patients. Recently it established CCH can activate inflammasome signaling pathways, involving NLRP3 AIM2 inflammasomes critically regulate IL-1β production. Given neuroinflammation early event important we understand its molecular cellular mechanisms enable development disease-modifying treatments reduce structural brain damage cognitive deficits are observed clinically elderly. Hence, this review aims provide comprehensive insight into involved pathogenesis CCH-induced VCI.

Язык: Английский

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The NLRP3 inflammasome in depression: Potential mechanisms and therapies

Pharmacological Research, Год журнала: 2022, Номер 187, С. 106625 - 106625

Опубликована: Дек. 21, 2022

Increasing evidence suggests that the failure of clinical antidepressants may be related with neuroinflammation. The NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome is an intracellular multiprotein complex, has been considered as a key contributor to development Inhibition NLRP3 effective method for depression treatment. In this review, we summarized current researches highlighting role in pathology depression. Firstly, discussed activation patients animal models. Secondly, outlined possible mechanisms driving inflammasome. Thirdly, pathogenetic Finally, overviewed potential targeting Overall, inhibition therapeutic strategy inflammation-related

Язык: Английский

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Mitochondrial dysfunction as a driver of NLRP3 inflammasome activation and its modulation through mitophagy for potential therapeutics

The International Journal of Biochemistry & Cell Biology, Год журнала: 2021, Номер 136, С. 106013 - 106013

Опубликована: Май 19, 2021

Язык: Английский

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Gut microbiome in Parkinson's disease: New insights from meta-analysis

Parkinsonism & Related Disorders, Год журнала: 2021, Номер 94, С. 1 - 9

Опубликована: Ноя. 17, 2021

Язык: Английский

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Inflammasome and Mitophagy Connection in Health and Disease

International Journal of Molecular Sciences, Год журнала: 2020, Номер 21(13), С. 4714 - 4714

Опубликована: Июль 1, 2020

The inflammasome is a large intracellular protein complex that activates inflammatory caspase-1 and induces the maturation of interleukin (IL)-1β IL-18. Mitophagy plays an essential role in maintenance mitochondrial homeostasis during stress. Previous studies have indicated compelling evidence crosstalk between mitophagy. regulation inflammasome, or vice versa, crucial for various biological functions, such as controlling inflammation metabolism, immune anti-tumor responses, pyroptotic cell death. Uncontrolled often results pathological pyroptosis, causes variety human diseases, including metabolic infection, cancer. Here, we discuss how improved understanding interactions mitophagy can lead to novel therapies against disease pathologies, inflammasome-mitophagy connection currently being targeted pharmacologically by diverse agents small molecules. A deeper will provide new insights into health through balance clearance pathology.

Язык: Английский

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Different Roles of Mitochondria in Cell Death and Inflammation: Focusing on Mitochondrial Quality Control in Ischemic Stroke and Reperfusion

Biomedicines, Год журнала: 2021, Номер 9(2), С. 169 - 169

Опубликована: Фев. 9, 2021

Mitochondrial dysfunctions are among the main hallmarks of several brain diseases, including ischemic stroke. An insufficient supply oxygen and glucose in cells, primarily neurons, triggers a cascade events which mitochondria leading characters. calcium overload, reactive species (ROS) overproduction, mitochondrial permeability transition pore (mPTP) opening, damage-associated molecular pattern (DAMP) release place center an intricate series chance interactions. Depending on degree to affected, they promote different pathways, ranging from inflammatory response pathways cell death pathways. In this review, we will explore principal mechanisms compromised during reperfusion injury, delineate potential neuroprotective strategies targeting dysfunction homeostasis.

Язык: Английский

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