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Simone, Roberta De; Ajmone‐Cat, Maria Antonietta; Carnevale, Daniela; Minghetti, Luisa

doi:10.1186/1742-2094-2-4

Cited by 216 publications

(76 citation statements)

References 57 publications

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“…The mechanisms behind class-switching are still not fully known. Cholinergic signaling through α7 nicotinic acetylcholine receptor (α7nAChR) has been suggested to stimulate a shift to pro-resolving LM production [45]. The deficiency in cholinergic signaling in the AD brain is well known.…”

Section: Discussionmentioning

confidence: 99%

Pro-Resolving Lipid Mediators Improve Neuronal Survival and Increase Aβ42 Phagocytosis

et al. 2015

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Inflammation in the brain is a prominent feature in Alzheimer’s disease (AD). Recent studies suggest that chronic inflammation can be a consequence of failure to resolve the inflammation. Resolution of inflammation is mediated by a family of lipid mediators (LMs), and the levels of these specialized pro-resolving mediators (SPMs) are reduced in the hippocampus of those with AD. In the present study we combined analysis of LMs in the entorhinal cortex (ENT) from AD patients with in vitro analysis of their direct effects on neurons and microglia. We probed ENT, an area affected early in AD pathogenesis, by liquid chromatography-tandem mass spectrometry (LC-MS-MS), and found that the levels of the SPMs maresin 1 (MaR1), protectin D1 (PD1) and resolvin (Rv) D5, were lower in ENT of AD patients as compared to age-matched controls, while levels of the pro-inflammatory prostaglandin D2 (PGD2) were higher in AD. In vitro studies showed that lipoxin A4 (LXA4), MaR1, RvD1 and protectin DX (PDX) exerted neuroprotective activity, and that MaR1 and RvD1 down-regulated Aβ42-induced inflammation in human microglia. MaR1 exerted a stimulatory effect on microglial uptake of Aβ42. Our findings give further evidence for a disturbance of the resolution pathway in AD, and indicate that stimulating this pathway is a promising treatment strategy for AD.

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Section: Discussionmentioning

confidence: 99%

Pro-Resolving Lipid Mediators Improve Neuronal Survival and Increase Aβ42 Phagocytosis

et al. 2015

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“…We hypothesized that NRG1, through its binding to the ErbB receptors may increase the transcription of α7nAChRs in microglia. This would have interesting implications in the regulation of inflammation as previous work indicates that increases in α7nAChR expression can lead to a decrease in TNF-α, a known stimulator of inflammation [1,30]. Here we have documented ErbB expression in three immortalized cell lines and shown that NRG1 induces the phosphotyrosylation of the ErbB4 receptor in these cells.…”

Section: Discussionmentioning

confidence: 61%

“…This signal initiates the synthesis of ACh by the efferent arm of the vagus nerve. ACh then presumably acts on macrophages via the α7nAChR, thereby decreasing TNF-α release [1,8,30,38]. A similar cholinergic system has been described in the brain with microglia [15].…”

Section: Discussionmentioning

confidence: 99%

Neuregulin Upregulates Microglial α7 Nicotinic Acetylcholine Receptor Expression in Immortalized Cell Lines: Implications for Regulating Neuroinflammation

2013

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Neuregulin, previously known as ARIA, is a signaling protein involved in cell survival, synaptic plasticity, cell communication and differentiation. Neuregulin has also been described as a potent inducer of acetylcholine receptor transcription in muscle and although both neuregulin and acetylcholine have been individually described to have neuroprotective roles, their relationship in the cholinergic anti-inflammatory pathway of the brain has not been examined. Using three cell lines, BV-2, EOC-20 and RAW 264.7, we investigated the role that neuregulin signaling through the Erb family of tyrosine kinases may play in the anti-inflammatory process mediated by the α7 nicotinic acetylcholine receptors. Here we show that ErbB4 is expressed in all of our cell lines and is phosphorylated upon treatment with neuregulin. Neuregulin treatment further increases the expression of α7 nicotinic acetylcholine receptors in the microglial lines tested. Given the central role of α7 nicotinic acetylcholine receptors in regulating system inflammation we analyzed the expression of several pro-inflammatory cytokines in our system. Using ELISAs for TNF-α and IL-6 we show that treatment with NRG can produce a nearly a 33% decrease in the levels of tumor necrosis factor-α secreted by activated microglia and a nearly 88% decrease in IL-6. Given these results we propose a neuroprotective role for neuregulin wherein it modulates the expression of TNF-α and thus inflammation in the CNS via the upregulation of α7 nicotinic acetylcholine receptor expression in microglia in vitro. We suggest that the disregulation of neuregulin expression may be pivotal in neurological disorders characterized by inflammation.

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“…They also eliminate apoptotic cells during CNS remodeling and maturation. As in the peripheral immune system, recent data has demonstrated that the interaction of microglia with phosphatidylserine-expressing apoptotic neurons abrogates the inflammatory cascade and facilitates the elimination of damaged neurons through anti-inflammatory and neuroprotective processes [27]. Additionally, microglia produce neurotrophic molecules that promote neuronal survival and promote neuronal precursor cell proliferation, possibly through MAPK, PI3/AKT and delta-Notch signaling pathways [28].…”

Section: Immunological Approaches To Neuro-degenerative Disease Theramentioning

confidence: 97%

Immunological Approaches to Prevent Neuronal Apoptosis During Neuroinflammation

Murphy¹,

Keating²,

Sheehan³

et al. 2005

CMCAIAA

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Neurodegeneration is set to increase in parallel with society's age demographics. With the increasing appreciation of the role played by apoptosis in neurodegeneration, much effort has gone into understanding key effectors in this process and to develop therapies that reduce neuronal apoptosis, thus preserving the integrity of the CNS. In contrast to peripheral apoptosis, inflammation is commonly seen to co-localize with apoptotic sites in the CNS however investigators are unsure whether inflammation is the primary cause for neuronal apoptosis induction or whether it is secondary. This current review highlights the role of apoptosis in neurodegenerative diseases, examines the evidence as to whether inflammation is a causative or consequential event in neuronal apoptosis and describes some of the immunological approaches that are currently in the clinic or being developed.

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Untitled

Cited by 216 publications

References 57 publications

Pro-Resolving Lipid Mediators Improve Neuronal Survival and Increase Aβ42 Phagocytosis

Pro-Resolving Lipid Mediators Improve Neuronal Survival and Increase Aβ42 Phagocytosis

Neuregulin Upregulates Microglial α7 Nicotinic Acetylcholine Receptor Expression in Immortalized Cell Lines: Implications for Regulating Neuroinflammation

Immunological Approaches to Prevent Neuronal Apoptosis During Neuroinflammation

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