The Inflammasome Adaptor Protein ASC in Plasma as a Biomarker of Early Cognitive Changes DOI Open Access
Brianna Cyr, Rosie E. Curiel, David Loewenstein

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(14), P. 7758 - 7758

Published: July 16, 2024

Dementia is a group of symptoms including memory loss, language difficulties, and other types cognitive functional impairments that affects 57 million people worldwide, with the incidence expected to double by 2040. Therefore, there an unmet need develop reliable biomarkers diagnose early brain so emerging interventions can be applied before degeneration. Here, we performed biomarker analyses for apoptosis-associated speck-like protein containing caspase recruitment domain (ASC), neurofilament light chain (NfL), glial fibrillary acidic (GFAP), amyloid-β 42/40 (Aβ42/40) ratio in plasma older adults. Participants had blood drawn at baseline underwent two annual clinical evaluations. The groups tested either cognitively normal on both evaluations (NN), year 1 but impaired 2 (NI), or (II). ASC was elevated NI compared NN II groups. Additionally, Aβ42 increased group. Importantly, area under curve (AUC) participants than 70 years old vs. 0.81, indicating promising detection decline.

Language: Английский

Inflammasomes in neurological disorders — mechanisms and therapeutic potential DOI
Kishore Aravind Ravichandran, Michael T. Heneka

Nature Reviews Neurology, Journal Year: 2024, Volume and Issue: 20(2), P. 67 - 83

Published: Jan. 9, 2024

Language: Английский

Citations

37
Inflammasome activation in traumatic brain injury and Alzheimer's disease DOI Creative Commons
Nathan H. Johnson, Juan Pablo de Rivero Vaccari, Helen M. Bramlett

et al.

Translational research, Journal Year: 2022, Volume and Issue: 254, P. 1 - 12

Published: Sept. 6, 2022

Language: Английский

Citations

51
Anti-Inflammatory Effects of Marine Bioactive Compounds and Their Potential as Functional Food Ingredients in the Prevention and Treatment of Neuroinflammatory Disorders DOI Creative Commons

Mohamed Elbandy

Molecules, Journal Year: 2022, Volume and Issue: 28(1), P. 2 - 2

Published: Dec. 20, 2022

Functional foods include enhanced, enriched, fortified, or whole that impart health benefits beyond their nutritional value, particularly when consumed as part of a varied diet on regular basis at effective levels. Marine sources can serve the various healthy and numerous functional food ingredients with biological effects be derived from these sources. Microalgae, macroalgae, crustaceans, fungi, bacteria fish, fish by-products are most common marine provide many potential including phenolic compounds, proteins peptides, polysaccharides. Neuroinflammation is closely linked initiation progression neurodegenerative diseases, Alzheimer's disease, Huntington's Parkinson's disease. Activation astrocytes microglia defense mechanism brain to counter damaged tissues detrimental pathogens, wherein chronic activation triggers neuroinflammation further exacerbate induce neurodegeneration. Currently, available therapeutic agents only symptomatic relief disorders no therapies stop slow down advancement Thereffore, natural compounds exert protective effect against have potential. Numerous chemical bioactive fatty acids, pigments, alkaloids, polysaccharides, already been isolated show anti-inflammatory properties, which in treatment prevention neuroinflammatory disorders. The marine-derived neurological covered this review.

Language: Английский

Citations

44
β2 integrin regulates neutrophil trans endothelial migration following traumatic brain injury DOI Creative Commons
Lei Li,

Ruilong Peng,

Cong Wang

et al.

Cell Communication and Signaling, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 8, 2025

Neutrophils are the first responders among peripheral immune cells to infiltrate central nervous system following a traumatic brain injury (TBI), triggering neuroinflammation that can exacerbate secondary tissue damage. The precise molecular controls dictate inflammatory behavior of neutrophils post-TBI, however, remain largely elusive. Our comprehensive analysis landscape surrounding trauma in TBI mice has revealed significant alteration abundance β2 integrin (ITGB2), predominantly expressed by and closely associated with responses. Using fluid percussion (FPI) mouse model, we investigated therapeutic efficacy Rovelizumab, an agent blocks ITGB2. treatment demonstrated improvements neurologic function mice, attenuating blood–brain barrier permeability, mitigating oxidative stress mediator release, enhancing cerebral perfusion. Moreover, ITGB2 blockade effectively limited adherence, migration, infiltration neutrophils, impeded formation neutrophil extracellular traps (NETs) upon their activation. Finally, it was mediates these effects mainly through its interaction intercellular adhesion molecule-1 (ICAM 1) endotheliocyte. These findings collectively illuminate as crucial switch governs adverse post-TBI could be targeted improve clinical outcome patients.

Language: Английский

Citations

1
From spreading depolarization to blood–brain barrier dysfunction: navigating traumatic brain injury for novel diagnosis and therapy DOI
Gerben van Hameren, Refat Aboghazleh, Ellen Parker

et al.

Nature Reviews Neurology, Journal Year: 2024, Volume and Issue: 20(7), P. 408 - 425

Published: June 17, 2024

Language: Английский

Citations

8
Elucidating PAR1 as a therapeutic target for delayed traumatic brain injury: Unveiling the PPAR-γ/Nrf2/HO-1/GPX4 axis to suppress ferroptosis and alleviate NLRP3 inflammasome activation in rats DOI
Amira A. El-Gazar, Ayman A. Soubh, Dalaal M. Abdallah

et al.

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 139, P. 112774 - 112774

Published: July 26, 2024

Language: Английский

Citations

8
Hydroxysafflor yellow a confers neuroprotection against acute traumatic brain injury by modulating neuronal autophagy to inhibit NLRP3 inflammasomes DOI
Zelin Lai, Cong Li,

Huihan Ma

et al.

Journal of Ethnopharmacology, Journal Year: 2023, Volume and Issue: 308, P. 116268 - 116268

Published: Feb. 25, 2023

Language: Английский

Citations

13
Proof-of-Principle Study of Inflammasome Signaling Proteins as Diagnostic Biomarkers of the Inflammatory Response in Parkinson’s Disease DOI Creative Commons
Erika d. l. R. M. Cabrera Ranaldi, Karen Nuytemans,

Anisley Martinez

et al.

Pharmaceuticals, Journal Year: 2023, Volume and Issue: 16(6), P. 883 - 883

Published: June 15, 2023

Parkinson's disease (PD) is a neurodegenerative disorder marked by the death of dopaminergic neurons in midbrain, accumulation α-synuclein aggregates, and motor deficits. A major contributor to neuronal loss neuroinflammation. The inflammasome multiprotein complex that perpetuates neuroinflammation disorders including PD. Increases proteins are associated with worsened pathology. Thus, inhibition inflammatory mediators has potential aid PD treatment. Here, we investigated signaling as biomarkers response Plasma from subjects healthy age-matched controls were evaluated for levels protein apoptosis-associated speck-like containing caspase recruitment domain (ASC), caspase-1, interleukin (IL)-18. This was carried out using Simple Plex technology identify changes blood subjects. area under curve (AUC) obtained through calculation receiver operating characteristics (ROC) obtain information on biomarker reliability traits. Additionally, completed stepwise regression selected lowest Akaike criterion (AIC) assess how caspase-1 ASC contribute IL-18 people demonstrated elevated ASC, when compared controls; each these found be promising inflammation Furthermore, determined significantly predict serve reliable provide significant contributions

Language: Английский

Citations

13
Modulation of Inflammatory Response by Electromagnetic Field Stimulation in Traumatic Brain Injury in Yucatan Swine DOI
Yssel Mendoza‐Marí, Vikrant Rai, Mohamed M. Radwan

et al.

Journal of Surgery and Research, Journal Year: 2024, Volume and Issue: 07(01)

Published: Jan. 1, 2024

Traumatic brain injury is a leading cause of disability and death worldwide represents high economic burden for families national health systems. After mechanical impact to the head, first stage damage comprising edema, physical damage, cell loss gives rise second phase characterized by glial activation, increased oxidative stress excitotoxicity, mitochondrial exacerbated neuroinflammatory state, among other molecular calamities. Inflammation strongly influences events involved in pathogenesis TBI. Therefore, several components inflammatory cascade have been targeted experimental therapies. Application Electromagnetic Field (EMF) stimulation has found be effective some conditions. However, its effect neuronal recovery after TBI not known. In this pilot study, Yucatan miniswine were subjected using controlled cortical approach. EMF via helmet was applied immediately or two days impact. Three weeks later, markers assessed tissues injured contralateral non-injured areas control EMF-treated animals histomorphometry, immunohistochemistry, RT-qPCR, Western blot, ELISA. Our results revealed that induced beneficial with preservation tissue morphology as well reduction at transcriptional translational levels. Immediate application showed better resolution inflammation. Although further studies are warranted, our findings contribute notion could an therapeutic approach patients.

Language: Английский

Citations

5
Genetic predisposition to Alzheimer's disease alters inflammasome activity after traumatic brain injury DOI Creative Commons
Nathan H. Johnson,

Nadine Kerr,

Juan Pablo de Rivero Vaccari

et al.

Translational research, Journal Year: 2023, Volume and Issue: 257, P. 66 - 77

Published: Feb. 8, 2023

Traumatic Brain Injury (TBI) is a major cause of death and disability in the US recognized risk factor for development Alzheimer's disease (AD). The relationship between these conditions not completely understood, but may share additive or synergistic pathological hallmarks that serve as novel therapeutic targets. Heightened inflammasome signaling plays critical role pathogenesis central nervous system injury (CNS) release apoptosis-associated speck-like protein containing caspase recruitment domain (ASC) speck from neurons activated microglia contribute significantly to TBI AD pathology. This study investigated whether after was augmented this pathway impacted biochemical neuropathological outcomes overall cognitive function. Five-month-old, 3xTg mice respective wild type controls were randomized underwent moderate controlled cortical impact (CCI) served sham/uninjured controls. Animals sacrificed at 1 hour, day, week assess acute pathology 12 weeks assessing ipsilateral cerebral cortex processed expression by immunoblotting. Mice evaluated behavior open field (3 days), object recognition (2 weeks), Morris water maze (6 weeks) testing TBI. There statistically significant increase proteins Caspase-1, Caspase-8, ASC, interleukin (IL)-1β both animals. At 1-day post injury, increases ASC IL-1β measured compared WT Behavioral showed injured had altered function when mice. Elevated Aβ seen hippocampus sham groups injury. Moreover, treatment with IC100, an anti-ASC monoclonal antibody, inhibited inflammasome, evidenced reduction 1-week These findings show response heightened genetically predisposed suggests exacerbate Thus, dampening offer approach

Language: Английский

Citations

12