Focus on the Role of the NLRP3 Inflammasome in Multiple Sclerosis: Pathogenesis, Diagnosis, and Therapeutics

Frontiers in Molecular Neuroscience, Journal Year: 2022, Volume and Issue: 15

Published: May 25, 2022

Neuroinflammation is initiated with an aberrant innate immune response in the central nervous system (CNS) and involved many neurological diseases. Inflammasomes are intracellular multiprotein complexes that can be used as platforms to induce maturation secretion of proinflammatory cytokines pyroptosis, thus playing a pivotal role neuroinflammation. Among inflammasomes, nucleotide-binding oligomerization domain-, leucine-rich repeat- pyrin domain-containing 3 (NLRP3) inflammasome well-characterized contributes diseases, such multiple sclerosis (MS), Alzheimer's disease (AD), ischemic stroke. MS chronic autoimmune CNS, its hallmarks include inflammation, demyelination, neurodegeneration. Studies have demonstrated relationship between NLRP3 inflammasome. To date, pathogenesis not fully understood, clinical studies on novel therapies still underway. Here, we review activation mechanism inflammasome, MS, targeting related molecules, which may beneficial MS.

Language: Английский

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Exosomes derived from programmed cell death: mechanism and biological significance

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: March 1, 2024

Abstract Exosomes are nanoscale extracellular vesicles present in bodily fluids that mediate intercellular communication by transferring bioactive molecules, thereby regulating a range of physiological and pathological processes. can be secreted from nearly all cell types, the biological function exosomes is heterogeneous depends on donor type state. Recent research has revealed levels released endosomal system increase cells undergoing programmed death. These play crucial roles diseases, such as inflammation, tumors, autoimmune diseases. However, there currently lack systematic differences biogenesis, secretion mechanisms, composition under different death modalities. This review underscores potential vital mediators processes, highlighting interconnection between exosome biosynthesis regulatory mechanisms governing Furthermore, we accentuate prospect leveraging for development innovative biomarkers therapeutic strategies across various

Language: Английский

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Inflammasome Molecular Insights in Autoimmune Diseases

Current Issues in Molecular Biology, Journal Year: 2024, Volume and Issue: 46(4), P. 3502 - 3532

Published: April 18, 2024

Autoimmune diseases (AIDs) emerge due to an irregular immune response towards self- and non-self-antigens. Inflammation commonly accompanies these conditions, with inflammatory factors inflammasomes playing pivotal roles in their progression. Key concepts molecular biology, inflammation, mimicry are crucial understanding AID development. Exposure foreign antigens can cause potentially leading AIDs through triggered by cross-reactive epitopes. Molecular emerges as a key mechanism which infectious or chemical agents trigger autoimmunity. In certain susceptible individuals, autoreactive T B cells may be activated antigen resemblances between self-peptides. Chronic typically driven abnormal responses, is strongly associated pathogenesis. Inflammasomes, vital cytosolic multiprotein complexes assembled infections stress, activating processes macrophages. characterized prolonged tissue injury repair cycles, significantly damage tissues, thereby increasing the risk of AIDs. Inhibiting inflammasomes, particularly autoinflammatory disorders, has garnered significant interest, pharmaceutical advancements targeting cytokines showing promise management.

Language: Английский

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Uncovering a new family of conserved virulence factors that promote the production of host‐damaging outer membrane vesicles in gram‐negative bacteria

Journal of Extracellular Vesicles, Journal Year: 2025, Volume and Issue: 14(1)

Published: Jan. 1, 2025

Abstract CprA is a short‐chain dehydrogenase/reductase (SDR) that contributes to resistance against colistin and antimicrobial peptides. The cprA gene conserved across Pseudomonas aeruginosa clades its expression directly regulated by the two‐component system PmrAB. We have shown leads production of outer membrane vesicles (OMVs) block autophagic flux greater capacity activate non‐canonical inflammasome pathway. In murine model sepsis, P. strain deleted for was less virulent than wild‐type (WT) strain. These results demonstrate important role in pathogenicity . It worth noting also functional ortholog hemolysin F (HlyF), which encoded virulence plasmids Escherichia coli other cryptic SDRs mammalian plant pathogens, such as Yersinia pestis Ralstonia solanacearum are orthologs HlyF. induce OMVs flux. This study uncovers new family determinants Gram‐negative bacteria, offering potential innovative therapeutic interventions deeper insights into bacterial pathogenesis.

Language: Английский

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Reframing the link between metabolism and NLRP3 inflammasome: therapeutic opportunities

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: July 20, 2023

Inflammasomes are multiprotein signaling platforms in the cytosol that senses exogenous and endogenous danger signals respond with maturation secretion of IL-1β IL-18 pyroptosis to induce inflammation protect host. The inflammasome best studied is Nucleotide-binding oligomerization domain, leucine-rich repeat-containing family pyrin domain containing 3 (NLRP3) inflammasome. It activated a two-step process: priming activation, leading sensor NLRP3 recruitment both adaptor ASC executioner pro-caspase 1, which by cleavage. Moreover, activation regulated posttranslational modifications, including ubiquitination/deubiquitination, phosphorylation/dephosphorylation, acetylation/deacetylation, SUMOylation nitrosylation, interaction NLPR3 protein binding partners. connection between it metabolism receiving increasing attention this field. In review, we present structure, functions, regulation NLRP3, special emphasis on mitochondrial dysfunction-mtROS production metabolic signals, i.e., metabolites as well enzymes. By understanding specific inhibitors can be rationally designed for treatment prevention various immune- or metabolic-based diseases. Lastly, review current their mechanism action.

Language: Английский

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To re-examine the intersection of microglial activation and neuroinflammation in neurodegenerative diseases from the perspective of pyroptosis

Frontiers in Aging Neuroscience, Journal Year: 2023, Volume and Issue: 15

Published: Nov. 9, 2023

Neurodegenerative diseases (NDs), such as Alzheimer’s disease, Parkinson’s Huntington’s and motor neuron are characterized by neuronal damage dysfunction. NDs considered to be a multifactorial disease with diverse etiologies (immune, inflammatory, aging, genetic, etc.) complex pathophysiological processes. Previous studies have found that neuroinflammation typical microglial activation important mechanisms of NDs, leading neurological dysfunction progression. Pyroptosis is new mode involved in this process. As form programmed cell death, pyroptosis the expansion cells until membrane bursts, resulting release contents activates strong inflammatory response promotes accelerating abnormal activation. In case, abnormally activated microglia various pro-inflammatory factors, occurrence exacerbating both pyroptosis, thus forming vicious cycle. The recognition association between activation, well neuroinflammation, significant importance understanding pathogenesis providing targets strategies for their prevention treatment.

Language: Английский

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The Role of the NLRP3 Inflammasome in HCC Carcinogenesis and Treatment: Harnessing Innate Immunity

Cancers, Journal Year: 2022, Volume and Issue: 14(13), P. 3150 - 3150

Published: June 27, 2022

The HCC constitutes one of the most frequent cancers, with a non-decreasing trend in disease mortality despite advances systemic therapy and surgery. This is fueled by rise an obesity wave which prominent Western populations has reshaped etiologic landscape HCC. Interest nucleotide-binding domain leucine-rich repeat containing (NLR) family member NLRP3 recently been revived since it would appear that, generating inflammasomes, participates several physiologic processes its dysfunction leads to disease. inflammasome studied depth, influence pathogenesis extensively documented during past quinquennial. Since inflammation comprises major regulator carcinogenesis, paramount importance attempt evaluate contribution generation management aim this review was examine literature order determine impact on, present hypothesis about input in,

Language: Английский

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A comprehensive insight into the immunomodulatory role of MSCs‐derived exosomes (MSC‐Exos) through modulating pattern‐recognition receptors (PRRs)

Cell Biochemistry and Function, Journal Year: 2024, Volume and Issue: 42(4)

Published: May 21, 2024

Mesenchymal stem cell-derived exosomes (MSC-Exos) are emerging as remarkable agents in the field of immunomodulation with vast potential for diagnosing and treating various diseases, including cancer autoimmune disorders. These tiny vesicles laden a diverse cargo encompassing proteins, nucleic acids, lipids, bioactive molecules, offering wealth biomarkers therapeutic options. MSC-Exos exhibit their immunomodulatory prowess by skillfully regulating pattern-recognition receptors (PRRs). They conduct symphony immunological responses, modulating B-cell activities, polarizing macrophages toward anti-inflammatory phenotypes, fine-tuning T-cell activity. interactions have profound implications precision medicine, immunotherapy, disease management, biomarker discovery, regulatory approvals. promises to usher new era tailored therapies, personalized diagnostics, more effective treatments medical conditions. As research advances, transformative healthcare becomes increasingly evident.

Language: Английский

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NLRP3 inflammasome: A potential therapeutic target to minimize renal ischemia/reperfusion injury during transplantation

Transplant Immunology, Journal Year: 2022, Volume and Issue: 75, P. 101718 - 101718

Published: Sept. 17, 2022

Language: Английский

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Host and Pathogen-Directed Therapies against Microbial Infections Using Exosome- and Antimicrobial Peptide-derived Stem Cells with a Special look at Pulmonary Infections and Sepsis

Stem Cell Reviews and Reports, Journal Year: 2023, Volume and Issue: 19(7), P. 2166 - 2191

Published: July 26, 2023

Language: Английский

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