Cerebral nitric oxide represses choroid plexus
            <scp>NF</scp>
            κB‐dependent gateway activity for leukocyte trafficking

Baruch, Kuti; Kertser, Alexander; Porat, Ziv; Schwartz, Michal

doi:10.15252/embj.201591468

Cited by 63 publications

(52 citation statements)

References 71 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…4b). As the NF-kB pathway has been reported to positively involved in neuroinflammation [41,42], we investigated the positive regulation of I-kappaB kinase/NF-kappaB signaling in this murine ischemiareperfusion model. Among the factors involved in this indicated pathway, CASP8 was markedly upregulated at the mRNA level in the retinas of mice subjected to RIR injury ( Fig.…”

Section: Casp8 Is Involved In Acute Glaucomamentioning

confidence: 99%

NLRP12 collaborates with NLRP3 and NLRC4 to promote pyroptosis inducing ganglion cell death of acute glaucoma

Chen

Deng

Gan

et al. 2020

Mol Neurodegeneration

100

View full text Add to dashboard Cite

Background: Acute glaucoma, characterized by a sudden elevation in intraocular pressure (IOP) and retinal ganglion cells (RGCs) death, is a major cause of irreversible blindness worldwide that lacks approved effective therapies, validated treatment targets and clear molecular mechanisms. We sought to explore the potential molecular mechanisms underlying the causal link between high IOP and glaucomatous RGCs death.Methods: A murine retinal ischemia/ reperfusion (RIR) model and an in vitro oxygen and glucose deprivation/ reoxygenation (OGDR) model were used to investigate the pathogenic mechanisms of acute glaucoma.Results: Our findings reveal a novel mechanism of microglia-induced pyroptosis-mediated RGCs death associated with glaucomatous vision loss. Genetic deletion of gasdermin D (GSDMD), the effector of pyroptosis, markedly ameliorated the RGCs death and retinal tissue damage in acute glaucoma. Moreover, GSDMD cleavage of microglial cells was dependent on caspase-8 (CASP8)-hypoxia-inducible factor-1α (HIF-1α) signaling. Mechanistically, the newly identified nucleotide-binding leucine-rich repeat-containing receptor (NLR) family pyrin domain-containing 12 (NLRP12) collaborated with NLR family pyrin domain-containing 3 (NLRP3) and NLR family CARD domain-containing protein 4 (NLRC4) downstream of the CASP8-HIF-1α axis, to elicit pyroptotic processes and interleukin-1β (IL-1β) maturation through caspase-1 activation, facilitating pyroptosis and neuroinflammation in acute glaucoma. Interestingly, processing of IL-1β in turn magnified the CASP8-HIF-1α-NLRP12/ NLRP3/NLRC4-pyroptosis circuit to accelerate inflammatory cascades.Conclusions: These data not only indicate that the collaborative effects of NLRP12, NLRP3 and NLRC4 on pyroptosis are responsible for RGCs death, but also shed novel mechanistic insights into microglial pyroptosis, paving novel therapeutic avenues for the treatment of glaucoma-induced irreversible vision loss through simultaneously targeting of pyroptosis.

show abstract

Section: Casp8 Is Involved In Acute Glaucomamentioning

confidence: 99%

NLRP12 collaborates with NLRP3 and NLRC4 to promote pyroptosis inducing ganglion cell death of acute glaucoma

Chen

Deng

Gan

et al. 2020

Mol Neurodegeneration

100

View full text Add to dashboard Cite

show abstract

“…The choroid plexus is a well-described gateway for leukocyte trafficking into the brain, with direct access to the ventricular CSF (Baruch and Schwartz, 2013; Herkenham, 2005; Sallusto et al, 2012). The Schwartz group has greatly expanded our understanding of T cell trafficking through the choroid plexus in chronic inflammation and aging models (Baruch et al, 2014; Baruch et al, 2015a; Baruch et al, 2013; Baruch et al, 2015b; Baruch and Schwartz, 2013). This group has also shown that acute exposure to predator odor stress caused a modest increase in lymphocyte trafficking into the choroid plexus (Lewitus et al, 2008).…”

Section: Mechanisms Of Immune-to-brain Influencementioning

confidence: 99%

Contributions of the adaptive immune system to mood regulation: Mechanisms and pathways of neuroimmune interactions

Herkenham

Kigar

2017

Progress in Neuro-Psychopharmacology and Biological Psychiatry

View full text Add to dashboard Cite

Clinical and basic studies of functional interactions between adaptive immunity, affective states, and brain function are reviewed, and the neural, humoral, and cellular routes of bidirectional communication between the brain and the adaptive immune system are evaluated. In clinical studies of depressed populations, lymphocytes—the principal cells of the adaptive immune system—exhibit altered T cell subtype ratios and CD4+ helper T cell polarization profiles. In basic studies using psychological stress to model depression, T cell profiles are altered as well, consistent with stress effects conveyed by the hypothalamic-pituitary-adrenal axis and sympathetic nervous system. Lymphocytes in turn have effects on behavior and CNS structure and function. CD4+ T cells in particular appear to modify affective behavior and rates of hippocampal dentate gyrus neurogenesis. These observations force the question of how such actions are carried out. CNS effects may occur via cellular and molecular mechanisms whereby effector memory T cells and the cytokine profiles they produce in the blood interact with the blood-brain barrier in ways that remain to be clarified. Understanding the mechanisms by which T cells polarize and interact with the brain to alter mood states is key to advances in the field, and may permit development of therapies that target cells in the periphery, thus bypassing problems associated with bioavailability of drugs within the brain.

show abstract

“…The b-term 'nitric oxide synthase' (i.e. NOS) [27] can be interpreted in view of microbiome contribution in NOS-mediated inflammation at gut level [28][29][30] [28][29][30].…”

Section: Resultsmentioning

confidence: 99%

Reducing the Search Space in Literature-Based Discovery by Exploring Outlier Documents: a Case Study in Finding Links Between Gut Microbiome and Alzheimer’s Disease

Cestnik

Fabbretti

Gubiani

et al. 2017

Genomics Comput Biol

View full text Add to dashboard Cite

Literature-based discovery tools have been often used to overcome the problem of fragmentation of science and to assist researchers in their process of cross-domain knowledge discovery.In this paper we propose a methodology for cross-domain literature-based discovery that focuses on outlier documents to reduce the search space of potential cross-domain links and to improve search efficiency. In a previous study, literature mining tools OntoGen for document clustering and CrossBee for cross-domain bridging term exploration were combined to search for hidden relations in scientific papers from two different domains of interest, where the utility of the approach was demonstrated in a study involving PubMed papers about Alzheimer's disease and gut microbiome. This paper extends the approach by proposing a methodology, implemented as a repeatable workflow in a web-based text mining platform TextFlows, which enables easy access and execution of the methodology for the interested researcher.

show abstract

Cerebral nitric oxide represses choroid plexus NF κB‐dependent gateway activity for leukocyte trafficking

Cited by 63 publications

References 71 publications

NLRP12 collaborates with NLRP3 and NLRC4 to promote pyroptosis inducing ganglion cell death of acute glaucoma

NLRP12 collaborates with NLRP3 and NLRC4 to promote pyroptosis inducing ganglion cell death of acute glaucoma

Contributions of the adaptive immune system to mood regulation: Mechanisms and pathways of neuroimmune interactions

Reducing the Search Space in Literature-Based Discovery by Exploring Outlier Documents: a Case Study in Finding Links Between Gut Microbiome and Alzheimer’s Disease

Contact Info

Product

Resources

About