The cellular response in neuroinflammation: The role of leukocytes, microglia and astrocytes in neuronal death and survival

Carson, Monica J.; Thrash, J. Cameron; Walter, Barbara

doi:10.1016/j.cnr.2006.09.004

Cited by 240 publications

(169 citation statements)

References 66 publications

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“…7A, the Epac agonist had a qualitatively similar effect on the mRNA levels of seven inflammatory mediators in resting microglia as had been previously shown for PGE 2 and butaprost (cf. Fig.…”

Section: Ep2 Activation Modulates Expression Of Inflammatory Mediatorsupporting

confidence: 75%

“…However, in traumatic brain injury, mice deficient for IL-6 showed increased oxidative stress, decreased cell survival, and delayed wound healing, indicating that IL-6 might also be protective (50). Here, we show that PGE 2 and EP2 activation by butaprost exacerbates the induction of COX-2, iNOS, and IL-6, which should promote inflammation caused by microglial activation, in classically activated microglia.…”

Section: Volume 288 • Number 13 • March 29 2013mentioning

confidence: 61%

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EP2 Receptor Signaling Pathways Regulate Classical Activation of Microglia

Quan

Jiang

Dingledine

2013

Journal of Biological Chemistry

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Background: Microglial activation contributes strongly to brain inflammation. Results: The modulation of microglial cyclooxygenase-2, iNOS, and cytokine production by EP2 (PTGER2) activation is not blocked by a protein kinase A antagonist but is mimicked by an Epac agonist. Conclusion: Epac signaling pathways prominently contribute to the modulation of microglial activation by EP2. Significance: EP2 and Epac represent potential immunomodulatory targets during brain inflammation.

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Section: Ep2 Activation Modulates Expression Of Inflammatory Mediatorsupporting

confidence: 75%

Section: Volume 288 • Number 13 • March 29 2013mentioning

confidence: 61%

EP2 Receptor Signaling Pathways Regulate Classical Activation of Microglia

Quan

Jiang

Dingledine

2013

Journal of Biological Chemistry

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“…T cells exposed to antigen can cross the intact brain-blood barrier and migrate into the brain (19,20). It has also been shown that immunologic reactions occur in the brain in response to a number of processes that affect the CNS and spinal cord (21). These findings encourage the development of immunotherapy for lesions of the CNS and the identification of tumor antigens.…”

Section: Discussionmentioning

confidence: 96%

NY-ESO-1 Expression in Meningioma Suggests a Rationale for New Immunotherapeutic Approaches

Baía

Caballero

et al. 2013

Cancer Immunology Research

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Meningiomas are the most common primary intracranial tumors. Surgical resection remains the treatment of choice for these tumors. However, a significant number of tumors are not surgically accessible, recur, or become malignant, necessitating the repetition of surgery and sometimes radiation. Chemotherapy is rarely used and is generally not recognized as an effective treatment. Cancer/testis (CT) genes represent a unique class of genes, which are expressed by germ cells, normally silenced in somatic cells, but activated in various cancers. CT proteins can elicit spontaneous immune responses in patients with cancer and this feature makes them attractive targets for immunotherapy-based approaches. We analyzed mRNA expression of 37 testis-restricted CT genes in a discovery set of 18 meningiomas by reverse transcription PCR. The overall frequency of expression of CT genes ranged from 5.6% to 27.8%. The most frequently expressed was NY-ESO-1, in 5 patients (27.8%). We subsequently analyzed NY-ESO-1 protein expression in a larger set of meningiomas by immunohistochemistry and found expression in 108 of 110 cases. In some cases, NY-ESO-1 expression was diffused and homogenous, but in most instances it was heterogeneous. Importantly, NY-ESO-1 expression was positively correlated with higher grade and patients presenting with higher levels of NY-ESO-1 staining had significantly worse disease-free and overall survival. We have also shown that NY-ESO-1 expression may lead to humoral immune response in patients with meningioma. Considering the limited treatment options for patients with meningioma, the potential of NY-ESO-1-based immunotherapy should be explored. Cancer Immunol Res; 1(5); 296-302. Ó2013 AACR.

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“…Neuroinflammatory mechanisms involving microglial activation, astrogliosis, and lymphocyte infiltration probably also contribute to the cascade of events leading to neuronal degeneration (Carson et al, 2006;Hirsch and Hunot, 2009;More et al, 2013) in several neurodegenerative disorders, such as AD, PD, HD, amyotrophic lateral sclerosis (ALS) and progressive supranuclear palsy (Hirsch and Hunot, 2009;Wright et al, 2013). Exposure to lipopolysaccharides induces neuroinflammation in mice and dopaminergic neuronal cultures, which further leads to dopaminergic neuronal death and accumulation of insoluble cytoplasmic inclusions of α-synuclein in nigral neurons.…”

Section: Role In Glial Cell Regulated Neuronal Degenerationmentioning

confidence: 99%

Rheb in neuronal degeneration, regeneration, and connectivity

Potheraveedu

Schöpel

Stoll

et al. 2017

Biological Chemistry

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Abstract:The small GTPase Rheb was originally detected as an immediate early response protein whose expression was induced by NMDA-dependent synaptic activity in the brain. Rheb's activity is highly regulated by its GTPase activating protein (GAP), the tuberous sclerosis complex protein, which stimulates the conversion from the active, GTP-loaded into the inactive, GDP-loaded conformation. Rheb has been established as an evolutionarily conserved molecular switch protein regulating cellular growth, cell volume, cell cycle, autophagy, and amino acid uptake. The subcellular localization of Rheb and its interacting proteins critically regulate its activity and function. In stem cells, constitutive activation of Rheb enhances differentiation at the expense of self-renewal partially explaining the adverse effects of deregulated Rheb in the mammalian brain. In the context of various cellular stress conditions such as oxidative stress, ER-stress, death factor signaling, and cellular aging, Rheb activation surprisingly enhances rather than prevents cellular degeneration. This review addresses cell type-and cell state-specific function(s) of Rheb and mainly focuses on neurons and their surrounding glial cells. Mechanisms will be discussed in the context of therapy that interferes with Rheb's activity using the antibiotic rapamycin or low molecular weight compounds.

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The cellular response in neuroinflammation: The role of leukocytes, microglia and astrocytes in neuronal death and survival

Cited by 240 publications

References 66 publications

EP2 Receptor Signaling Pathways Regulate Classical Activation of Microglia

EP2 Receptor Signaling Pathways Regulate Classical Activation of Microglia

NY-ESO-1 Expression in Meningioma Suggests a Rationale for New Immunotherapeutic Approaches

Rheb in neuronal degeneration, regeneration, and connectivity

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