The Neglected Sibling: NLRP2 Inflammasome in the Nervous System DOI Open Access
László Ducza, Botond Gaál

Published: Nov. 14, 2023

While classical NOD-like receptor pyrin domain containing protein 1 (NLRP1) and NLRP3 inflammasomal proteins have been extensively investigated, the contribution of NLRP2 is still ill-defined in nervous system. Given putative significance orchestrating neuroinflammation, further inquiry needed to gain a better understanding its connectome, hence specific targeting may hold promising therapeutic implication. Therefore, bioinformatical approach for extracting information, specifically context neuropathologies, also undoubtedly preferred. To best our knowledge, there no review study selectively only NLRP2. Increasing, but fragmentary evidence should encourage researchers thoroughly investigate this inflammasome various animal- human models. Taken together, herein we aimed current literature focusing on role system more importantly, provide an algorythm-based network elucidating potentially valuable molecular partnerships.

Language: Английский

Immunological dimensions of neuroinflammation and microglial activation: exploring innovative immunomodulatory approaches to mitigate neuroinflammatory progression DOI Creative Commons
Lucas Fornari Laurindo, Jefferson Aparecido Dias, Adriano Cressoni Araújo

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 8, 2024

The increasing life expectancy has led to a higher incidence of age-related neurodegenerative conditions. Within this framework, neuroinflammation emerges as significant contributing factor. It involves the activation microglia and astrocytes, leading release pro-inflammatory cytokines chemokines infiltration peripheral leukocytes into central nervous system (CNS). These instances result in neuronal damage neurodegeneration through activated nucleotide-binding domain leucine-rich repeat containing (NLR) family pyrin protein 3 (NLRP3) nuclear factor kappa B (NF-kB) pathways decreased erythroid 2-related 2 (Nrf2) activity. Due limited effectiveness regarding inhibition neuroinflammatory targets using conventional drugs, there is challenging growth search for innovative therapies alleviating CNS diseases or even before their onset. Our results indicate that interventions focusing on Interleukin-Driven Immunomodulation, Chemokine (CXC) Receptor Signaling Expression, Cold Exposure, Fibrin-Targeted strategies significantly promise mitigate processes. approaches demonstrate potential anti-neuroinflammatory effects, addressing conditions such Multiple Sclerosis, Experimental autoimmune encephalomyelitis, Parkinson’s Disease, Alzheimer’s Disease. While findings are promising, immunomodulatory often face limitations due Immune-Related Adverse Events. Therefore, conduction randomized clinical trials matter mandatory, will pave way promising future development new medicines with specific therapeutic targets.

Language: Английский

Citations

47
A Decade of Dedication: Pioneering Perspectives on Neurological Diseases and Mental Illnesses DOI Creative Commons
Masaru Tanaka, László Vécsei

Biomedicines, Journal Year: 2024, Volume and Issue: 12(5), P. 1083 - 1083

Published: May 13, 2024

Welcome to

Language: Английский

Citations

17
Anti-Inflammatory Role of the Klotho Protein and Relevance to Aging DOI Creative Commons
Gérald J. Prud’homme, Qinghua Wang

Cells, Journal Year: 2024, Volume and Issue: 13(17), P. 1413 - 1413

Published: Aug. 24, 2024

The α-Klotho protein (hereafter Klotho) is an obligate coreceptor for fibroblast growth factor 23 (FGF23). It produced in the kidneys, brain and other sites. Klotho insufficiency causes hyperphosphatemia anomalies. Importantly, it associated with chronic pathologies (often age-related) that have inflammatory component. This includes atherosclerosis, diabetes Alzheimer's disease. Its mode of action these diseases not well understood, but inhibits or regulates multiple major pathways. has a membrane form soluble (s-Klotho). Cytosolic postulated characterized. s-Klotho endocrine properties are incompletely elucidated. binds to FGF receptor 1c (FGFR1c) widely expressed (including endothelial cells). also attaches FGF23, FGF23/Klotho FGFRs. Thus, might be roaming FGF23 coreceptor, functions. Notably, (cell-bound soluble) counteracts inflammation appears mitigate related aging (inflammaging). NF-κB NLRP3 inflammasome. inflammasome requires priming by produces active IL-1β, pores cell death (pyroptosis). In accord, countered injury induced toxins, damage-associated molecular patterns (DAMPs), cytokines, reactive oxygen species (ROS). blocks TGF-β Wnt ligands, which lessens fibrotic Low loss muscle mass (sarcopenia), as occurs diseases. counters inhibitory effects myostatin on muscle, reduces inflammation, improves repair following injury. inhibition factors may protective diabetic retinopathy age-related macular degeneration (AMD). review examines functions especially potential applications.

Language: Английский

Citations

10
Role of Peripheral NLRP3 Inflammasome in Cognitive Impairments: Insights of Non-central Factors DOI
Min Qiao, Junjun Ni,

Hong Qing

et al.

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

Language: Английский

Citations

1
MicroRNA-7 attenuates secondary brain injury following experimental intracerebral hemorrhage via inhibition of NLRP3 DOI
Bo Luo, Lin Li, Xu-Dong Song

et al.

Journal of Stroke and Cerebrovascular Diseases, Journal Year: 2024, Volume and Issue: 33(5), P. 107670 - 107670

Published: March 2, 2024

Language: Английский

Citations

5
The impact of neuroinflammation on neuronal integrity DOI Open Access
Bora Tastan, Michael T. Heneka

Immunological Reviews, Journal Year: 2024, Volume and Issue: 327(1), P. 8 - 32

Published: Oct. 1, 2024

Neuroinflammation, characterized by a complex interplay among innate and adaptive immune responses within the central nervous system (CNS), is crucial in responding to infections, injuries, disease pathologies. However, dysregulation of neuroinflammatory response could significantly affect neurons terms function structure, leading profound health implications. Although tremendous progress has been made understanding relationship between processes alterations neuronal integrity, specific implications concerning both structure have not extensively covered, with exception perspectives on glial activation neurodegeneration. Thus, this review aims provide comprehensive overview multifaceted interactions key inflammatory players, exploring mechanisms through which inflammation influences functionality structural integrity CNS. Further, it will discuss how these lead impairment functions architecture highlight consequences caused dysregulated functions, such as cognitive dysfunction mood disorders. By integrating insights from recent research findings, enhance our landscape set stage for future interventions that transform current approaches preserve CNS-related conditions.

Language: Английский

Citations

5
Carvacrol attenuated haloperidol-induced Parkinson’s disease via TNF/NFκβ-NLRP3-mediated pyroptosis DOI Creative Commons
Faisal F. Albaqami, K Ahmad, Fawad Ali Shah

et al.

Laboratory Animal Research, Journal Year: 2025, Volume and Issue: 41(1)

Published: Feb. 5, 2025

Abstract Background Parkinson’s disease is a debilitating and the second most common neurodegenerative disorder with high prevalence. has multifaceted etiology characterized by an altered redox state excessive inflammatory response. In this study, we investigated potential neuroprotective properties of carvacrol in haloperidol-induced model. female Sprague-Dawley rats, animal Parkinson model was induced intraperitoneally administering 1 mg / kg haloperidol once daily for fifteen days. Carvacrol administered at dose 25 50 days before administration. order to further illustrate vital role tumor necrosis factor (TNF-α) pathway, TNF-α inhibitor thalidomide 15 Results Our results showed that motor deficits, changed endogenous antioxidant enzymes, along higher levels inflammasome (NLRP3) other mediators. Moreover, increased lipid peroxidase (LPO) indicated significant rise oxidative stress due haloperidol. reduced these effects preventing pyroptosis mediated TNF-α. The administration mitigated suppresses pathways through augmentation intrinsic system. Further, co-treatment synergized effect as demonstrated various immunoassays histology analyses. Conclusions Taken together, our findings suggest Parkinson-like symptoms, partially downregulation NLRP3.

Language: Английский

Citations

0
The Impact of Chronic Diseases on Cognitive Impairment in Rural Population of India: A Focus on Diabetes, Hypertension, Cardiovascular Disease, and Stroke DOI Creative Commons
J. Ramesh, Anish Mehta, Krishnamurthy Jayanna

et al.

Brain Behavior and Immunity Integrative, Journal Year: 2025, Volume and Issue: unknown, P. 100107 - 100107

Published: Feb. 1, 2025

Language: Английский

Citations

0
A molecular systems architecture of neuromuscular junction in amyotrophic lateral sclerosis DOI Creative Commons

V. A. Shiva Ayyadurai,

Prabhakar Deonikar,

Roger D. Kamm

et al.

npj Systems Biology and Applications, Journal Year: 2025, Volume and Issue: 11(1)

Published: March 17, 2025

A molecular systems architecture is presented for the neuromuscular junction (NMJ) in order to provide a framework organizing complexity of biomolecular interactions amyotrophic lateral sclerosis (ALS) using systematic literature review process. ALS fatal motor neuron disease characterized by progressive degeneration upper and lower neurons that supply voluntary muscles. The contains cells such as neurons, skeletal muscle cells, astrocytes, microglia, Schwann endothelial which are implicated pathogenesis ALS. This provides multi-layered understanding intra- inter-cellular microenvironment, may be utilized target identification, discovery single combination therapeutics, clinical strategies treat

Language: Английский

Citations

0
Acute and long-term cognitive impairment following sepsis: mechanism and prevention DOI
Mu‐Huo Ji,

Yu-Zhu Gao,

Cui-na Shi

et al.

Expert Review of Neurotherapeutics, Journal Year: 2023, Volume and Issue: 23(10), P. 931 - 943

Published: Aug. 24, 2023

ABSTRACTIntroduction Sepsis is a severe host response to infection, which induces both acute and long-term cognitive impairment. Despite its high incidence following sepsis, the underlying mechanisms remain elusive effective treatments are not available clinically.Area covered This review focuses on elucidating pathological impairment sepsis. Specifically, authors discuss role of systemic inflammation response, blood–brain barrier disruption, neuroinflammation, mitochondrial dysfunction, neuronal Aβ accumulation tau phosphorylation in after Additionally, they current strategies ameliorate impairment.Expert opinion Potential interventions reduce sepsis include earlier diagnosis infection control, hemodynamic homeostasis, adequate brain perfusion. Furthermore, inflammatory reactive oxygen species, injury or death could be beneficial. Implementing minimize delirium, sleep disturbance, stress factors, immobility also recommended. avoiding neurotoxins implementing early rehabilitation may important for preventing sepsis.KEYWORDS: Sepsiscognitive impairmentpathological mechanismsoutcomesinterventions Article highlights impairments.The sepsis-induced fully understood.Effective therapeutics clinically.Interventions associated with might stabilizing hemodynamics perfusion.Interventions attenuate inflammation, beneficial.Avoiding crucial.Abbreviations BBB=Blood-brain barrier;BDNF=brain-derived neurotrophic factor;CLP=Cecum ligation puncture;CNS=Central nervous system;EEG=Electroencephalogram;HMGB1=High mobility group protein 1;HMG-CoA=Hydroxymethylglutaryl coenzyme A;HO-1=Heme oxygenase-1;ICU=Intensive care unit;IFNs=Interferons;IL=Interleukin;LPS=Lipopolysaccharide;MMPs=Matrix metalloproteinases;NOX2=NADPH oxidase isoform 2;NF-κB=Nuclear factor kappa B;NLRP3=Nucleotide-binding domain-like receptor protein3;NRG1=Neuregulin-1;Nrf2=Nuclear erythroid-2 related factor;proBDNF=precursor form brain-derived factor;PV=parvalbumin;ROS=Reactive species;SAE=Sepsis-associated encephalopathy;TLRs=Toll-like receptors.Declaration interestThe have no other relevant affiliations financial involvement any organization entity interest conflict subject matter materials discussed manuscript apart from those disclosed.Reviewer disclosuresPeer reviewers this relationships disclose.Additional informationFundingThis work was supported by grants National Natural Science Foundation China (81971892 & 82172131).

Language: Английский

Citations

10