Inflammasome assembly in neurodegenerative diseases

Trends in Neurosciences, Год журнала: 2023, Номер 46(10), С. 814 - 831

Опубликована: Авг. 24, 2023

Язык: Английский

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Parkin regulates microglial NLRP3 and represses neurodegeneration in Parkinson's disease

Aging Cell, Год журнала: 2023, Номер 22(6)

Опубликована: Апрель 7, 2023

Abstract Microglial hyperactivation of the NOD‐, LRR‐, and pyrin domain‐containing 3 (NLRP3) inflammasome contributes to pathogenesis Parkinson's disease (PD). Recently, neuronally expressed NLRP3 was demonstrated be a Parkin polyubiquitination substrate driver neurodegeneration in PD. However, role activation microglia remains unclear. Thus, we aimed investigate whether regulates microglia. We investigated through overexpression BV2 microglial cells knockout primary after lipopolysaccharide (LPS) treatment. Immunoprecipitation experiments were conducted quantify ubiquitination levels under various conditions assess interaction between NLRP3. In vivo by administering intraperitoneal injections LPS wild‐type mice. The Rotarod test, pole open field test performed evaluate motor functions. Immunofluorescence for pathological detection key proteins. Overexpression mediated degradation via K48‐linked loss activity LPS‐induced mice resulted excessive assembly, facilitating impairment, dopaminergic neuron substantia nigra. Accelerating Parkin‐induced administration heat shock protein (HSP90) inhibitor reduced inflammatory response. alleviates These results suggest that targeting Parkin‐mediated could potential therapeutic strategy

Язык: Английский

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Targeting NLRP3 inflammasome for neurodegenerative disorders

Molecular Psychiatry, Год журнала: 2023, Номер 28(11), С. 4512 - 4527

Опубликована: Сен. 5, 2023

Язык: Английский

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Role of NLRP3 inflammasome-mediated neuronal pyroptosis and neuroinflammation in neurodegenerative diseases

Inflammation Research, Год журнала: 2023, Номер 72(9), С. 1839 - 1859

Опубликована: Сен. 1, 2023

Язык: Английский

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Role of pyroptosis in the pathogenesis and treatment of diseases

MedComm, Год журнала: 2023, Номер 4(3)

Опубликована: Апрель 25, 2023

Abstract Programmed cell death (PCD) is regarded as a pathological form of with an intracellular program mediated, which plays pivotal role in maintaining homeostasis and embryonic development. Pyroptosis new paradigm PCD, has received increasing attention due to its close association immunity disease. inflammatory mediated by gasdermin that promotes the release proinflammatory cytokines contents induced inflammasome activation. Recently, evidence studies shows pyroptosis crucial conditions like cardiovascular diseases (CVDs), cancer, neurological (NDs), metabolic (MDs), suggesting targeting potential intervention for treatment these diseases. Based on this, review aims identify molecular mechanisms signaling pathways related activation summarizes current insights into complicated relationship between multiple human (CVDs, NDs, MDs). We also discuss promising novel strategy method treating focus pathway application clinics.

Язык: Английский

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Chaperone‐mediated autophagy: Molecular mechanisms, biological functions, and diseases

MedComm, Год журнала: 2023, Номер 4(5)

Опубликована: Авг. 30, 2023

Chaperone-mediated autophagy (CMA) is a lysosomal degradation pathway that eliminates substrate proteins through heat-shock cognate protein 70 recognition and lysosome-associated membrane type 2A-assisted translocation. It distinct from macroautophagy microautophagy. In recent years, the regulatory mechanisms of CMA have been gradually enriched, including newly discovered NRF2 p38-TFEB signaling, as positive negative pathways CMA, respectively. Normal activity involved in regulation metabolism, aging, immunity, cell cycle, other physiological processes, while dysfunction may be occurrence neurodegenerative disorders, tumors, intestinal atherosclerosis, so on, which provides potential targets for treatment prediction related diseases. This article describes general process its role activities summarizes connection between macroautophagy. addition, human diseases concern or protective are discussed. Our review deepens understanding functions summary past research vision future directions.

Язык: Английский

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NLRP3 Inflammasome’s Activation in Acute and Chronic Brain Diseases—An Update on Pathogenetic Mechanisms and Therapeutic Perspectives with Respect to Other Inflammasomes

Biomedicines, Год журнала: 2023, Номер 11(4), С. 999 - 999

Опубликована: Март 23, 2023

Increasingly prevalent acute and chronic human brain diseases are scourges for the elderly. Besides lack of therapies, these ailments share a neuroinflammation that is triggered/sustained by different innate immunity-related protein oligomers called inflammasomes. Relevant players such as microglia/monocytes typically exhibit strong NLRP3 inflammasome activation. Hence idea suppression might solve neurodegenerative ailments. Here we review recent Literature about this topic. First, update conditions mechanisms, including RNAs, extracellular vesicles/exosomes, endogenous compounds, ethnic/pharmacological agents/extracts regulating function. Second, pinpoint NLRP3-activating mechanisms known inhibition effects in (ischemia, stroke, hemorrhage), (Alzheimer’s disease, Parkinson’s Huntington’s MS, ALS), virus-induced (Zika, SARS-CoV-2, others) diseases. The available data show (i) disease-specific divergent activate (mainly animal) brains NLRP3; (ii) no evidence proves modifies (yet ad hoc trials ongoing); (iii) findings exclude concurrently activated other-than-NLRP3 inflammasomes functionally replace inhibited NLRP3. Finally, highlight among causes persistent therapies species difference problem disease models preference symptomatic over etiologic therapeutic approaches. Therefore, posit neural cell-based could drive etiological, pathogenetic, advances, NLRP3’s other inflammasomes’ regulation, while minimizing failure risks candidate drug trials.

Язык: Английский

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Parthanatos: Mechanisms, modulation, and therapeutic prospects in neurodegenerative disease and stroke

Biochemical Pharmacology, Год журнала: 2024, Номер 228, С. 116174 - 116174

Опубликована: Март 27, 2024

Язык: Английский

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Pyroptosis-mediator GSDMD promotes Parkinson’s disease pathology via microglial activation and dopaminergic neuronal death

Brain Behavior and Immunity, Год журнала: 2024, Номер 119, С. 129 - 145

Опубликована: Март 27, 2024

Язык: Английский

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Novel insights into Parkin-mediated mitochondrial dysfunction and neuroinflammation in Parkinson's disease

Current Opinion in Neurobiology, Год журнала: 2023, Номер 80, С. 102720 - 102720

Опубликована: Апрель 5, 2023

Mutations in PRKN cause the second most common genetic form of Parkinson's disease (PD)-a debilitating movement disorder that is on rise due to population aging industrial world.PRKN codes for an E3 ubiquitin ligase has been well established as a key regulator mitophagy.Together with PTEN-induced kinase 1 (PINK1), Parkin controls lysosomal degradation depolarized mitochondria.But Parkin's functions go beyond mitochondrial clearance: versatile protein involved mitochondria-derived vesicle formation, cellular metabolism, calcium homeostasis, DNA maintenance, biogenesis, and apoptosis induction.Moreover, can act modulator different inflammatory pathways.In current review, we summarize latest literature concerning diverse roles maintaining healthy pool.Moreover, discuss how these recent discoveries may translate into personalized therapeutic approaches not only PRKN-PD patients but also subset idiopathic cases.

Язык: Английский

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