Neuroinflammation

Bazán, Nicolás G.; Halabi, Anasheh; Ertel, Monica; Petasis, Nicos A.

doi:10.1016/b978-0-12-374947-5.00034-1

Cited by 22 publications

(18 citation statements)

References 85 publications

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“…Interestingly, inflammation pathways such as “interferon signaling” (activation z-score = 3.441, p -value = 1.8 × 10 −12 ) and “neuroinflammation signaling” (activation z-score = 5.461, p -value = 5.1 × 10 −9 ) were also found among the top pathways ( Figure 2 d). The latter describes the process of how microglia control homeostasis in the central nervous system which generally serves a neuroprotective role and is described by expression of pro-inflammatory cytokines [ 40 ]. Individual upregulated genes upon YBX1 KD associated with this pathway include several apoptosis-related inflammatory genes such as FAS , TNF , several caspases (e.g., CASP8 ) and MHC class I genes.…”

Section: Resultsmentioning

confidence: 99%

YBX1 Indirectly Targets Heterochromatin-Repressed Inflammatory Response-Related Apoptosis Genes through Regulating CBX5 mRNA

Kloetgen

Duggimpudi

Schuschel

et al. 2020

IJMS

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Medulloblastomas arise from undifferentiated precursor cells in the cerebellum and account for about 20% of all solid brain tumors during childhood; standard therapies include radiation and chemotherapy, which oftentimes come with severe impairment of the cognitive development of the young patients. Here, we show that the posttranscriptional regulator Y-box binding protein 1 (YBX1), a DNA- and RNA-binding protein, acts as an oncogene in medulloblastomas by regulating cellular survival and apoptosis. We observed different cellular responses upon YBX1 knockdown in several medulloblastoma cell lines, with significantly altered transcription and subsequent apoptosis rates. Mechanistically, PAR-CLIP for YBX1 and integration with RNA-Seq data uncovered direct posttranscriptional control of the heterochromatin-associated gene CBX5; upon YBX1 knockdown and subsequent CBX5 mRNA instability, heterochromatin-regulated genes involved in inflammatory response, apoptosis and death receptor signaling were de-repressed. Thus, YBX1 acts as an oncogene in medulloblastoma through indirect transcriptional regulation of inflammatory genes regulating apoptosis and represents a promising novel therapeutic target in this tumor entity.

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Section: Resultsmentioning

confidence: 99%

YBX1 Indirectly Targets Heterochromatin-Repressed Inflammatory Response-Related Apoptosis Genes through Regulating CBX5 mRNA

Kloetgen

Duggimpudi

Schuschel

et al. 2020

IJMS

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“…NPD1 modulates neuroinflammatory signaling and reduces oxidative stress-induced apoptosis by modulating pro-inflammatory gene expression and the Bcl-2 family of proteins [ 18 , 56 ]. Also, since BDNF, NGF, NT3 and other neurotrophins are NPD1-synthesis agonists, this survival mechanism might potentiate neurotrophin activity [ 57 ].…”

Section: Discussionmentioning

confidence: 99%

“…DHA-derived docosanoids mediate neuroprotective bioactivity [ 18 ]. The stereoselective mediator neuroprotectin D1 (NPD1; 10 R ,17 S -dihydroxy-docosa-4 Z ,7 Z ,11 E ,13 E ,15 Z ,19 Z -hexaenoic acid) has been shown to attenuate damage resulting from ischemia-reperfusion [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

“…The stereoselective mediator neuroprotectin D1 (NPD1; 10 R ,17 S -dihydroxy-docosa-4 Z ,7 Z ,11 E ,13 E ,15 Z ,19 Z -hexaenoic acid) has been shown to attenuate damage resulting from ischemia-reperfusion [ 19 ]. NPD1 promotes cell survival and homeostasis regulation during cellular damage [ 18 ]. Hippocampal NPD1 pool size increases after seizures [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

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Hippocampal Neuro-Networks and Dendritic Spine Perturbations in Epileptogenesis Are Attenuated by Neuroprotectin D1

et al. 2015

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PurposeLimbic epileptogenesis triggers molecular and cellular events that foster the establishment of aberrant neuronal networks that, in turn, contribute to temporal lobe epilepsy (TLE). Here we have examined hippocampal neuronal network activities in the pilocarpine post-status epilepticus model of limbic epileptogenesis and asked whether or not the docosahexaenoic acid (DHA)-derived lipid mediator, neuroprotectin D1 (NPD1), modulates epileptogenesis.MethodsStatus epilepticus (SE) was induced by intraperitoneal administration of pilocarpine in adult male C57BL/6 mice. To evaluate simultaneous hippocampal neuronal networks, local field potentials were recorded from multi-microelectrode arrays (silicon probe) chronically implanted in the dorsal hippocampus. NPD1 (570 μg/kg) or vehicle was administered intraperitoneally daily for five consecutive days 24 hours after termination of SE. Seizures and epileptiform activity were analyzed in freely-moving control and treated mice during epileptogenesis and epileptic periods. Then hippocampal dendritic spines were evaluated using Golgi-staining.ResultsWe found brief spontaneous microepileptiform activity with high amplitudes in the CA1 pyramidal and stratum radiatum in epileptogenesis. These aberrant activities were attenuated following systemic NPD1 administration, with concomitant hippocampal dendritic spine protection. Moreover, NPD1 treatment led to a reduction in spontaneous recurrent seizures.ConclusionsOur results indicate that NPD1 displays neuroprotective bioactivity on the hippocampal neuronal network ensemble that mediates aberrant circuit activity during epileptogenesis. Insight into the molecular signaling mediated by neuroprotective bioactivity of NPD1 on neuronal network dysfunction may contribute to the development of anti-epileptogenic therapeutic strategies.

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“…This process occurs both in white matter and grey matter [ 150 ], which results in disruption of axonal transmission causing motor and sensory impairments [ 149 ]. Though the precise molecular events that lead to MS are unknown, inflammatory anomalies, a key phenomenon in the disease pathology, result in the breakdown of the blood–brain barrier vascular endothelium affecting myelin and oligodendrocytes [ 151 , 152 ]. Further, activation of lymphocytes, macrophages, dendritic cells, and microglia are observed at the onset of the disease [ 153 , 154 ].…”

Section: Neuroinflammation and Potential Of Cholinergic Allosterismentioning

confidence: 99%

Allosterism of Nicotinic Acetylcholine Receptors: Therapeutic Potential for Neuroinflammation Underlying Brain Trauma and Degenerative Disorders

Mitra

Khatri

Maulik

et al. 2020

IJMS

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Inflammation is a key physiological phenomenon that can be pervasive when dysregulated. Persistent chronic inflammation precedes several pathophysiological conditions forming one of the critical cellular homeostatic checkpoints. With a steady global surge in inflammatory diseases, it is imperative to delineate underlying mechanisms and design suitable drug molecules targeting the cellular partners that mediate and regulate inflammation. Nicotinic acetylcholine receptors have a confirmed role in influencing inflammatory pathways and have been a subject of scientific scrutiny underlying drug development in recent years. Drugs designed to target allosteric sites on the nicotinic acetylcholine receptors present a unique opportunity to unravel the role of the cholinergic system in regulating and restoring inflammatory homeostasis. Such a therapeutic approach holds promise in treating several inflammatory conditions and diseases with inflammation as an underlying pathology. Here, we briefly describe the potential of cholinergic allosterism and some allosteric modulators as a promising therapeutic option for the treatment of neuroinflammation.

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Neuroinflammation

Cited by 22 publications

References 85 publications

YBX1 Indirectly Targets Heterochromatin-Repressed Inflammatory Response-Related Apoptosis Genes through Regulating CBX5 mRNA

YBX1 Indirectly Targets Heterochromatin-Repressed Inflammatory Response-Related Apoptosis Genes through Regulating CBX5 mRNA

Hippocampal Neuro-Networks and Dendritic Spine Perturbations in Epileptogenesis Are Attenuated by Neuroprotectin D1

Allosterism of Nicotinic Acetylcholine Receptors: Therapeutic Potential for Neuroinflammation Underlying Brain Trauma and Degenerative Disorders

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