Roles for NF-κB in nerve cell survival, plasticity, and disease

Mattson, Mark P.; Meffert, Mollie K.

doi:10.1038/sj.cdd.4401837

Cited by 519 publications

(416 citation statements)

References 100 publications

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“…Of the secreted neurohumoral substances, PDGF, IGF, TGF-β1 and IL-10 have critical roles in preventing neural apoptosis via the PI3K-Akt/NF-κB pathway [20][21][22]37 . Nerve growth factor and BDNF prevent activation of the mitochondrial apoptotic pathway via the P75NTR-mediated NF-κB pathway 23,38 . NF-κB activation induces the upregulation of anti-apoptotic genes, including Bcl-2 and Bcl-xL 20,23, and the Akt pathway could independently block the mitochondrial apoptotic pathway 23 .…”

Section: Discussionmentioning

confidence: 99%

Direct isolation and RNA-seq reveal environment-dependent properties of engrafted neural stem/progenitor cells

et al. 2012

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neural stem/progenitor cell (nsPC) transplantation is a promising treatment for various neurodegenerative disorders including spinal cord injury, however, no direct analysis has ever been performed on their in vivo profile after transplantation. Here we combined bioimaging, flow-cytometric isolation and ultra-high-throughput RnA sequencing to evaluate the cellular properties of engrafted nsPCs. The acutely transplanted nsPCs had beneficial effects on spinal cord injury, particularly neuroprotection and neurohumoral secretion, whereas their in situ secretory activity differed significantly from that predicted in vitro. The RnA-sequencing of engrafted nsPCs revealed dynamic expression/splicing changes in various genes involved in cellular functions and tumour development depending on graft environments. notably, in the pathological environment, overall transcriptional activity, external signal transduction and neural differentiation of engrafted nsPCs were significantly suppressed. These results highlight the vulnerability of engrafted nsPCs to environmental force, while emphasizing the importance of in situ analysis in advancing the efficacy and safety of stem cell-based therapies.

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Section: Discussionmentioning

confidence: 99%

Direct isolation and RNA-seq reveal environment-dependent properties of engrafted neural stem/progenitor cells

et al. 2012

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“…159 The reasons for these discrepancies are not clear, but may stem from the fact that NF-B has prosurvival effects in neurons and other cell types. 160 Nevertheless, microglial NF-B activation in brain ischemia appears to be largely neurotoxic.…”

Section: Nf-b and Ap-1mentioning

confidence: 99%

Microglial Activation in Stroke: Therapeutic Targets

2010

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Summary:Microglial activation is an early response to brain ischemia and many other stressors. Microglia continuously monitor and respond to changes in brain homeostasis and to specific signaling molecules expressed or released by neighboring cells. These signaling molecules, including ATP, glutamate, cytokines, prostaglandins, zinc, reactive oxygen species, and HSP60, may induce microglial proliferation and migration to the sites of injury. They also induce a nonspecific innate immune response that may exacerbate acute ischemic injury. This innate immune response includes release of reactive oxygen species, cytokines, and proteases. Microglial activation requires hours to days to fully develop, and thus presents a target for therapeutic intervention with a much longer window of opportunity than acute neuroprotection. Effective agents are now available for blocking both microglial receptor activation and the microglia effector responses that drive the inflammatory response after stroke. Effective agents are also available for targeting the signal transduction mechanisms linking these events. However, the innate immune response can have beneficial as well deleterious effects on outcome after stoke, and a challenge will be to find ways to selectively suppress the deleterious effects of microglial activation after stroke without compromising neurovascular repair and remodeling.

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“…Nuclear factor kappa B (NFκB) is another non-histone substrate for acetylation; its function in synaptic plasticity and several types of LTM has previously been established and reviewed elsewhere [192,193]. Interestingly, in cultured cells, it was shown that CBP and p300 acetylate the NFκB p65 subunit in a stimulus-dependent manner, which, subsequently, could be deacetylated through HDAC3.…”

Section: Non-histone Protein Acetylation In Synaptic Plasticity and Mmentioning

confidence: 99%

Acetyltransferases (HATs) as Targets for Neurological Therapeutics

et al. 2013

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The acetylation of histone and non-histone proteins controls a great deal of cellular functions, thereby affecting the entire organism, including the brain. Acetylation modifications are mediated through histone acetyltransferases (HAT) and deacetylases (HDAC), and the balance of these enzymes regulates neuronal homeostasis, maintaining the pre-existing acetyl marks responsible for the global chromatin structure, as well as regulating specific dynamic acetyl marks that respond to changes and facilitate neurons to encode and strengthen longterm events in the brain circuitry (e.g., memory formation). Unfortunately, the dysfunction of these finely-tuned regulations might lead to pathological conditions, and the deregulation of the HAT/HDAC balance has been implicated in neurological disorders. During the last decade, research has focused on HDAC inhibitors that induce a histone hyperacetylated state to compensate acetylation deficits. The use of these inhibitors as a therapeutic option was efficient in several animal models of neurological disorders. The elaboration of new cell-permeant HAT activators opens a new era of research on acetylation regulation. Although pathological animal models have not been tested yet, HAT activator molecules have already proven to be beneficial in ameliorating brain functions associated with learning and memory, and adult neurogenesis in wild-type animals. Thus, HAT activator molecules contribute to an exciting area of research.

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Roles for NF-κB in nerve cell survival, plasticity, and disease

Cited by 519 publications

References 100 publications

Direct isolation and RNA-seq reveal environment-dependent properties of engrafted neural stem/progenitor cells

Direct isolation and RNA-seq reveal environment-dependent properties of engrafted neural stem/progenitor cells

Microglial Activation in Stroke: Therapeutic Targets

Acetyltransferases (HATs) as Targets for Neurological Therapeutics

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