complex(GO:"NF-kappaB complex")
We observed that anatabine dose dependently inhibited NFκB activation by TNFα in HEK293 NFκB luciferase reporter cells (Fig. 5) whereas nicotine was ineffective PubMed:21958873
In addition, an inhibition of p65 NFκB phosphorylation was observed following treatment with anatabine in 7W CHO overexpressing APP (Fig. 6A), in HEK293 (Fig. 6B) and in human neuronal like SH-SY5Y cells (Fig. 6C) showing that anatabine can prevent NFκB activation in various cell lines. PubMed:21958873
Since BACE-1 transcription is regulated by NFκB (Buggia-Prevot et al., 2008) and since we have shown that anatabine inhibits NFκB activation, we investigated the effect of anatabine on BACE-1 transcription using human neuronal like SH-SY5Y cells PubMed:21958873
Since anatabine lowers NFκB activation in vitro, we explored the possibility that anatabine may affect the level of C-reactive protein (CRP) whose expression is NFκB dependent (Karlsen et al., 2010; Yang et al.,2010). PubMed:21958873
We observed that anatabine dose dependently inhibited NFκB activation by TNFα in HEK293 NFκB luciferase reporter cells (Fig. 5) whereas nicotine was ineffective PubMed:21958873
We observed that anatabine dose dependently inhibited NFκB activation by TNFα in HEK293 NFκB luciferase reporter cells (Fig. 5) whereas nicotine was ineffective PubMed:21958873
In addition, we verified that pharmacological inhibition of Syk with BAY61-3606 resulted in a blockade of NFkB activation and that genetic down-regulation of SYK using shRNA also prevented NFkB activation (data not shown) thus highlighting Syk as a key player of NFkB activation. PubMed:25331948
PMA is a known agonist of PKC, which leads to the activation of the PKC/RAS/RAF/MEK/MAPK pathway that ultimately induces NFkB activation (46–48) PubMed:25331948
The magnitude of the NFkB inhibition following (-)-nilvadipine treatment was also reduced in clones of HEK293 NFkB luciferase reporter cells in which Syk expression had been silenced (data not shown) further suggesting that Syk is required to mediate the inhibition of NFkB activity induced by (-)-nilvadipine. PubMed:25331948
Tyrosine kinases, including Syk and Bruton’s tyrosine kinase (BTK), are activated following PMA treatment (49, 50), act upstream of RAS/RAF (51, 52), and mediate the activation of the NFkB pathway (53). PubMed:25331948
In addition, we verified that pharmacological inhibition of Syk with BAY61-3606 resulted in a blockade of NFkB activation and that genetic down-regulation of SYK using shRNA also prevented NFkB activation (data not shown) thus highlighting Syk as a key player of NFkB activation. PubMed:25331948
The magnitude of the NFkB inhibition following (-)-nilvadipine treatment was also reduced in clones of HEK293 NFkB luciferase reporter cells in which Syk expression had been silenced (data not shown) further suggesting that Syk is required to mediate the inhibition of NFkB activity induced by (-)-nilvadipine. PubMed:25331948
Weobserved that (-)-nilvadipine inhibits NFkB activation in response to TNFα (Fig. 4A) or phorbol 12-myristate 13-acetate (PMA) (Fig. 4B) by using an NFkB-luciferase reporter cell line to monitor NFkB activation, thus suggesting a possible mechanism responsible for the inhibition of BACE-1 transcription following nilvadipine treatment PubMed:25331948
Weobserved that (-)-nilvadipine inhibits NFkB activation in response to TNFα (Fig. 4A) or phorbol 12-myristate 13-acetate (PMA) (Fig. 4B) by using an NFkB-luciferase reporter cell line to monitor NFkB activation, thus suggesting a possible mechanism responsible for the inhibition of BACE-1 transcription following nilvadipine treatment PubMed:25331948
For instance, the small GTPase Rho and its downstream effector Rho-associated coiled-coil containing protein kinase (ROCK) have been shown to contribute to TNFα induction of NFkB activation (45). PubMed:25331948
For instance, the small GTPase Rho and its downstream effector Rho-associated coiled-coil containing protein kinase (ROCK) have been shown to contribute to TNFα induction of NFkB activation (45). PubMed:25331948
Tyrosine kinases, including Syk and Bruton’s tyrosine kinase (BTK), are activated following PMA treatment (49, 50), act upstream of RAS/RAF (51, 52), and mediate the activation of the NFkB pathway (53). PubMed:25331948
NF-κB and STAT3 are the major transcription factors activated by IL-1 and OSM, respectively PubMed:25681350
NF-κB and STAT3 are the major transcription factors activated by IL-1 and OSM, respectively PubMed:25681350
Since TNF also efficiently activates NF-κB, we tested whether, similarly to IL-1, TNF regulates YKL-40 expression by a RelB-dependent mechanism. PubMed:25681350
Recent evidence has cogently shown that Amyloid-β induces apoptosis in rat primary neurons and human post-mitotic neuronal cells by reducing Bcl-XL expression level and evoking the release of cytochrome c from the mitochondria in a NF-κB – dependent manner PubMed:28745240
Furthermore, fibrillar Amyloid-β has been shown to activate NF-κB via the assembly pf the C5b-MAC complex PubMed:28745240
Furthermore, Amyloid-β actuates NF-κB – dependent pro-inflammatory pathways in microglia culminating in TNFα expression and subsequently TNFα effectuated neurotoxicity PubMed:28745240
In primary neuronal cultures, Amyloid-β has been shown to elicit oxidative stress and evoke NF-κB activation PubMed:28745240
Furthermore, Amyloid-β –induced NF-κB also results in the up-regulation of the antioxidant mitochondrial membrane enzyme – MnSOD (superoxide dismutase 2) [328] which is well known to combat oxidative stress and apoptosis PubMed:28745240
Furthermore, nitric oxide (NO), a well characterized repressor of NF-κB activation and signaling [174, 175], causes a mitigation in neurogenesis PubMed:28745240
Physiological, pathophysiological, and biochemical stimuli known to induce proliferation of NPC via NF-κB activation include cerebral infarction [165], traumatic brain injury [166], reactive oxygen species [167], hypoxia [168-172], sAPPα [147], and sphingosine-1-phosphate [173] PubMed:28745240
Physiological, pathophysiological, and biochemical stimuli known to induce proliferation of NPC via NF-κB activation include cerebral infarction [165], traumatic brain injury [166], reactive oxygen species [167], hypoxia [168-172], sAPPα [147], and sphingosine-1-phosphate [173] PubMed:28745240
Additionally, NF-κB activity is also actuated by glutamate- mediated excitatory neurotransmission in the hippocampus, cerebral cortex, and the cerebellar granule cells PubMed:28745240
Consequently, NF-κB is constitutively activated in the excitatory neurons of the cerebral cortex (layers 2, 4, and 5), hippocampus (granule and pyramidal neurons of CA1 and CA3), and cerebellar granule cells and this constitutive activity is indispensable for neuronal survival in response to glutamate-induced excitotoxicity PubMed:28745240
The molecular mechanism underlying constitutive activation of NF-κB by glutamate-induced excitatory synaptic neurotransmission has been ascribed to NMDA receptor mediated Ca2+ influx and subsequent activation of CaMKII PubMed:28745240
Moreover, NF-κB mediates the NSC migration in response to physiological and pathophysiological stimuli such as cerebral cortex injury [181], seizure [182], and ischemic stroke PubMed:28745240
Emerging evidence has implicated Amyloid-β in augmenting cytosolic Ca2+ levels and causing NF- κB activation via calcineurin in astrocytes PubMed:28745240
Amyloid-β has also been demonstrated to induce apoptosis via the JNK1/c-Jun/Fas ligand signaling cascade [110], which results in NF-κB activation PubMed:28745240
Amyloid-β has also been demonstrated to induce apoptosis via the JNK1/c-Jun/Fas ligand signaling cascade [110], which results in NF-κB activation PubMed:28745240
Amyloid-β induced apoptosis has also been ascribed to dyshomeostasis of intracellular Ca2+ and oxidative stress [106-108], two critical biochemical derangements known to activate NF-κB PubMed:28745240
The molecular mechanism underlying constitutive activation of NF-κB by glutamate-induced excitatory synaptic neurotransmission has been ascribed to NMDA receptor mediated Ca2+ influx and subsequent activation of CaMKII PubMed:28745240
The three well characterized sensors of intracellular calcium – calmodulin/CamKII pathway, PI3K/ Akt pathway, and protein kinase C (PKC) pathway – are known to induce NF-κB activation and couple upstream signal transduction pathways that induce calcium dyshomeostasis to NF-κB activation PubMed:28745240
Moreover, there is preponderance of data implicating Amyloid-β in the modulation of PKC signaling pathway [335-338] and the PI3K/Akt/mTOR signaling pathway [339-341], which are known to activate NF-κB signaling pathway PubMed:28745240
Amyloid-β induced apoptosis has also been ascribed to dyshomeostasis of intracellular Ca2+ and oxidative stress [106-108], two critical biochemical derangements known to activate NF-κB PubMed:28745240
NF-κB acts as a sensor of oxidative stress and it is well established that oxidative stress results in the activation of NF-κB PubMed:28745240
In primary neuronal cultures, Amyloid-β has been shown to elicit oxidative stress and evoke NF-κB activation PubMed:28745240
In addition to CamKII, other kinases activated in response to a rise in cytosolic Ca2+ such as protein kinase C (PKC), phosphatidylinositol-3-kinase (PI3K), and Akt, also activate NF-κB signaling pathway by increasing the phosphorylation and activation of IKK PubMed:28745240
There is evidence that Amyloid-β causes the activation of Ca2+/calmodulin/CamKII pathway [332-334], thereby potentially leading to NF-κB activation. PubMed:28745240
In addition to CamKII, other kinases activated in response to a rise in cytosolic Ca2+ such as protein kinase C (PKC), phosphatidylinositol-3-kinase (PI3K), and Akt, also activate NF-κB signaling pathway by increasing the phosphorylation and activation of IKK PubMed:28745240
Furthermore, fibrillar Amyloid-β has been shown to activate NF-κB via the assembly pf the C5b-MAC complex PubMed:28745240
In addition to CamKII, other kinases activated in response to a rise in cytosolic Ca2+ such as protein kinase C (PKC), phosphatidylinositol-3-kinase (PI3K), and Akt, also activate NF-κB signaling pathway by increasing the phosphorylation and activation of IKK PubMed:28745240
In addition to CamKII, other kinases activated in response to a rise in cytosolic Ca2+ such as protein kinase C (PKC), phosphatidylinositol-3-kinase (PI3K), and Akt, also activate NF-κB signaling pathway by increasing the phosphorylation and activation of IKK PubMed:28745240
The three well characterized sensors of intracellular calcium – calmodulin/CamKII pathway, PI3K/ Akt pathway, and protein kinase C (PKC) pathway – are known to induce NF-κB activation and couple upstream signal transduction pathways that induce calcium dyshomeostasis to NF-κB activation PubMed:28745240
Moreover, there is preponderance of data implicating Amyloid-β in the modulation of PKC signaling pathway [335-338] and the PI3K/Akt/mTOR signaling pathway [339-341], which are known to activate NF-κB signaling pathway PubMed:28745240
Physiological, pathophysiological, and biochemical stimuli known to induce proliferation of NPC via NF-κB activation include cerebral infarction [165], traumatic brain injury [166], reactive oxygen species [167], hypoxia [168-172], sAPPα [147], and sphingosine-1-phosphate [173] PubMed:28745240
Both, brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) promote neurite outgrowth, in a NF- κB - dependent manner, in primary cultures of nodose ganglion sensory neurons from developing mice PubMed:28745240
Both, brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) promote neurite outgrowth, in a NF- κB - dependent manner, in primary cultures of nodose ganglion sensory neurons from developing mice PubMed:28745240
The molecular mechanism underlying constitutive activation of NF-κB by glutamate-induced excitatory synaptic neurotransmission has been ascribed to NMDA receptor mediated Ca2+ influx and subsequent activation of CaMKII PubMed:28745240
The three well characterized sensors of intracellular calcium – calmodulin/CamKII pathway, PI3K/ Akt pathway, and protein kinase C (PKC) pathway – are known to induce NF-κB activation and couple upstream signal transduction pathways that induce calcium dyshomeostasis to NF-κB activation PubMed:28745240
NF-κB positively regulates the transcription of interleukin 6 (IL6) family of cytokines such as IL6, leukemia inhibitory factor (LIF) and ciliary neurotrophic factor (CNTF) [184], which in-turn induce the differentiation of NSC into astrocytes by activating transcription factors STAT3, AP-1, and NF-κB itself PubMed:28745240
The trophic factors that evoke proliferation of NPC by inducing activation of NF-κB include epidermal growth factor (EGF) [155-161], basic fibroblast growth factor (bFGF) [155-161], vascular endothelial growth factor (VEGF) [162], tumor necrosis factor α (TNFα) [163], and erythropoietin (EPO) PubMed:28745240
The trophic factors that evoke proliferation of NPC by inducing activation of NF-κB include epidermal growth factor (EGF) [155-161], basic fibroblast growth factor (bFGF) [155-161], vascular endothelial growth factor (VEGF) [162], tumor necrosis factor α (TNFα) [163], and erythropoietin (EPO) PubMed:28745240
NF-κB positively regulates the transcription of interleukin 6 (IL6) family of cytokines such as IL6, leukemia inhibitory factor (LIF) and ciliary neurotrophic factor (CNTF) [184], which in-turn induce the differentiation of NSC into astrocytes by activating transcription factors STAT3, AP-1, and NF-κB itself PubMed:28745240
NF-κB positively regulates the transcription of interleukin 6 (IL6) family of cytokines such as IL6, leukemia inhibitory factor (LIF) and ciliary neurotrophic factor (CNTF) [184], which in-turn induce the differentiation of NSC into astrocytes by activating transcription factors STAT3, AP-1, and NF-κB itself PubMed:28745240
The mechanism underlying the effect of BDNF and CNTF on NF-κB activation has been attributed to the activation of Src and Lck non-receptor tyrosine kinases which phosphorylate IκBα on Tyr42 resulting in subsequent NF-κB activation PubMed:28745240
Furthermore, negative regulators of NF-κB such as the NAD+- dependent histone deacetylase – SIRT1, abolish the deleterious neurotoxic effects of Amyloid-β PubMed:28745240
The trophic factors that evoke proliferation of NPC by inducing activation of NF-κB include epidermal growth factor (EGF) [155-161], basic fibroblast growth factor (bFGF) [155-161], vascular endothelial growth factor (VEGF) [162], tumor necrosis factor α (TNFα) [163], and erythropoietin (EPO) PubMed:28745240
The trophic factors that evoke proliferation of NPC by inducing activation of NF-κB include epidermal growth factor (EGF) [155-161], basic fibroblast growth factor (bFGF) [155-161], vascular endothelial growth factor (VEGF) [162], tumor necrosis factor α (TNFα) [163], and erythropoietin (EPO) PubMed:28745240
Moreover, NF-κB mediates the NSC migration in response to physiological and pathophysiological stimuli such as cerebral cortex injury [181], seizure [182], and ischemic stroke PubMed:28745240
Moreover, NF-κB mediates the NSC migration in response to physiological and pathophysiological stimuli such as cerebral cortex injury [181], seizure [182], and ischemic stroke PubMed:28745240
Physiological, pathophysiological, and biochemical stimuli known to induce proliferation of NPC via NF-κB activation include cerebral infarction [165], traumatic brain injury [166], reactive oxygen species [167], hypoxia [168-172], sAPPα [147], and sphingosine-1-phosphate [173] PubMed:28745240
Physiological, pathophysiological, and biochemical stimuli known to induce proliferation of NPC via NF-κB activation include cerebral infarction [165], traumatic brain injury [166], reactive oxygen species [167], hypoxia [168-172], sAPPα [147], and sphingosine-1-phosphate [173] PubMed:28745240
Physiological, pathophysiological, and biochemical stimuli known to induce proliferation of NPC via NF-κB activation include cerebral infarction [165], traumatic brain injury [166], reactive oxygen species [167], hypoxia [168-172], sAPPα [147], and sphingosine-1-phosphate [173] PubMed:28745240
In neuronal cells Aβ1-42 peptide has been shown to regulate APP and BACE1 proteins in NF-κB dependent manner PubMed:25652642
Excessive accumulation of Aβ1-42 stimulates microglial cells by signaling via receptor associated advanced glycation end products (RAGE) and peroxisome proliferator-activated receptor-γ (PPAR-γ), phosphorylates IKK proteins, and enhances NF-κB mediated transactivation of inflammatory cytokines and neurotoxic molecules such as glutamate and reactive oxygen species (ROS)/induced nitric oxide synthase (iNOS) [12] (Fig 2B) PubMed:25652642
Under physiological conditions activation of NF-κB by endogenous Aβ reduces βAPP, BACE1 and the γ-secretase activity, thereby lowering Aβ processing and facilitating Aβ homeostasis PubMed:25652642
However in AD, exposure to high Aβ concentrations upregulates NF-κB activation increasing βAPP and Aβ processing, precipitating a feed-back loop that favor exacerbated Aβ production PubMed:25652642
Mechanistically, the Aβ induced neuronal apoptosis has been attributed to the increase in the ratio of proapoptotic gene (BAX) transcription to that of the anti-apoptotic gene Bcl-Xl, and/or to the reduction in constitutively activated NF-κB with consequent increase in the cytoplasmic IκB proteins PubMed:25652642
This is supported by the observation that in mixed neuronal-glial cell cultures, Aβ induces increasing degree of neurotoxicity in an NF-κB dependent manner in the presence of higher proportion of glial cells PubMed:25652642
A consequence of intracellular and parenchymal accumulation of NPs and NFTs is activation of NF-κB in the neural and glial cells with subsequent protective or detrimental effects PubMed:25652642
Unlike neurons, NF-κB is present in the cytoplasm as an inactive complex with the IκB proteins in glial cells under physiological conditions PubMed:25652642
In primary neuronal cells, exposure to Aβ25-35 peptide increase NF-κB mediated transactivation of manganese superoxide dismutase (Mn-SOD), suppress peroxinitrite production and inhibit membrane depolarization, thereby preventing apoptosis induced by oxidative stress PubMed:25652642
Several kinase pathways including the calcium-calmodium dependent kinase-II (CaMK), the protein kinases-C (PKC) and the ras/phosphatidylinositol 3-kinase (PI3K) pathways have been implicated in activating neuronal NF-κB signaling PubMed:25652642
A number of physiological stimuli including membrane depolarization or glutamergic signal transduction lead to rapid activation of the inducible NF-κB localized in the synapses, cytoplasm and dendrites of the neurons PubMed:25652642
Several kinase pathways including the calcium-calmodium dependent kinase-II (CaMK), the protein kinases-C (PKC) and the ras/phosphatidylinositol 3-kinase (PI3K) pathways have been implicated in activating neuronal NF-κB signaling PubMed:25652642
A number of physiological stimuli including membrane depolarization or glutamergic signal transduction lead to rapid activation of the inducible NF-κB localized in the synapses, cytoplasm and dendrites of the neurons PubMed:25652642
However in AD, exposure to high Aβ concentrations upregulates NF-κB activation increasing βAPP and Aβ processing, precipitating a feed-back loop that favor exacerbated Aβ production PubMed:25652642
Several kinase pathways including the calcium-calmodium dependent kinase-II (CaMK), the protein kinases-C (PKC) and the ras/phosphatidylinositol 3-kinase (PI3K) pathways have been implicated in activating neuronal NF-κB signaling PubMed:25652642
However in AD, exposure to high Aβ concentrations upregulates NF-κB activation increasing βAPP and Aβ processing, precipitating a feed-back loop that favor exacerbated Aβ production PubMed:25652642
Aβ has been shown to upregulate APOE in astroglial cells. This upregulation was inhibited by decoy-κB nucleotides supporting a critical role for NFκB in APOE function PubMed:25652642
These observations substantiate a direct role of neuronal NF–κB activation in the pathogenesis of AD PubMed:25652642
Increased presence of activated glial cells presenting elevated NF-κB and HLA-DR expression are commonly observed around the Aβ plaques in postmortem AD tissue PubMed:25652642
Increased presence of NF-κB mediated IL-1β, IL-6, and TNF-α cytokines have been reported in the affected tissues, serum and CSF of AD patients PubMed:25652642
A consequence of intracellular and parenchymal accumulation of NPs and NFTs is activation of NF-κB in the neural and glial cells with subsequent protective or detrimental effects PubMed:25652642
Increased presence of activated glial cells presenting elevated NF-κB and HLA-DR expression are commonly observed around the Aβ plaques in postmortem AD tissue PubMed:25652642
Since BACE-1 transcription is regulated by NFκB (Buggia-Prevot et al., 2008) and since we have shown that anatabine inhibits NFκB activation, we investigated the effect of anatabine on BACE-1 transcription using human neuronal like SH-SY5Y cells PubMed:21958873
Since anatabine lowers NFκB activation in vitro, we explored the possibility that anatabine may affect the level of C-reactive protein (CRP) whose expression is NFκB dependent (Karlsen et al., 2010; Yang et al.,2010). PubMed:21958873
As (-)-nilvadipine and racemic nilvadipine inhibit BACE-1 transcription, we evaluated whether (-)-nilvadipine was impacting NFkB activation because NFkB has been shown to play an important role in the regulation of BACE-1 transcription and expression (36, 37, 43, 44) PubMed:25331948
The indispensable role of NF-κB in synaptic transmission is corroborated by the fact that the mice that are deficient in neuronal p65, exhibit severe deficits in hippocampal basal synaptic transmission and long term potentiation (LTP) PubMed:28745240
Given the indispensable role of NF-κB proteins in synaptic transmission and synaptic plasticity, it is not surprising that NF-κB is plays an indispensable role in cognition and behavior as well PubMed:28745240
Consequently, NF-κB is constitutively activated in the excitatory neurons of the cerebral cortex (layers 2, 4, and 5), hippocampus (granule and pyramidal neurons of CA1 and CA3), and cerebellar granule cells and this constitutive activity is indispensable for neuronal survival in response to glutamate-induced excitotoxicity PubMed:28745240
Preponderance of evidence has implicated NF-κB as a survival factor in neurons [24, 114, 115] primarily because of the ability of NF-κB to suppress apoptosis in response to excitotoxic and apoptotic stimuli PubMed:28745240
Inhibition of NF-κB activity using a κB decoy DNA that results in the sequestration of NF-κB, increases the susceptibility of hippocampal neurons to noxious and apoptotic stimuli PubMed:28745240
NF-κB activation also protects hippocampal neurons from oxidative stress-induced apoptosis by inducing manganese superoxide dismutase (MnSOD) expression and mitigating peroxynitrite-induced protein nitration PubMed:28745240
Given the indispensable role of NF-κB proteins in synaptic transmission and synaptic plasticity, it is not surprising that NF-κB is plays an indispensable role in cognition and behavior as well PubMed:28745240
Given the indispensable role of NF-κB proteins in synaptic transmission and synaptic plasticity, it is not surprising that NF-κB is plays an indispensable role in cognition and behavior as well PubMed:28745240
Given the indispensable role of NF-κB proteins in synaptic transmission and synaptic plasticity, it is not surprising that NF-κB is plays an indispensable role in cognition and behavior as well PubMed:28745240
NF-κB is also indispensable for longterm spatial memory as assessed by radial arm maze [25] and Morris water maze paradigms in mice PubMed:28745240
The molecular mechanisms underlying the aforementioned involvement of NF-κB proteins in learning and memory have not been completely comprehended, although recent evidence has implicated NF-κB – induced transcriptional activation of Protein Kinase A (PKA) catalytic subunit that culminates in activation of CREB (cyclic AMP-response element binding protein) signaling [77] which is regarded as the molecular switch that converts short-term memory to long-term memory PubMed:28745240
The molecular mechanisms underlying the aforementioned involvement of NF-κB proteins in learning and memory have not been completely comprehended, although recent evidence has implicated NF-κB – induced transcriptional activation of Protein Kinase A (PKA) catalytic subunit that culminates in activation of CREB (cyclic AMP-response element binding protein) signaling [77] which is regarded as the molecular switch that converts short-term memory to long-term memory PubMed:28745240
The molecular mechanisms underlying the aforementioned involvement of NF-κB proteins in learning and memory have not been completely comprehended, although recent evidence has implicated NF-κB – induced transcriptional activation of Protein Kinase A (PKA) catalytic subunit that culminates in activation of CREB (cyclic AMP-response element binding protein) signaling [77] which is regarded as the molecular switch that converts short-term memory to long-term memory PubMed:28745240
Recent evidence has cogently shown that Amyloid-β induces apoptosis in rat primary neurons and human post-mitotic neuronal cells by reducing Bcl-XL expression level and evoking the release of cytochrome c from the mitochondria in a NF-κB – dependent manner PubMed:28745240
This is counter-intuitive as it is established that NF-κB positively regulates the expression of Bcl-XL and other members of the Bcl2 family PubMed:28745240
The anti-apoptotic effects of NF-κB have been ascribed to its ability to trans-activate the expression of a multitude of anti-apoptotic genes such as Bcl-2, Bcl-XL, and Bfl-1/A1 in the neurons of the amygdala, olfactory bulb, and the CA1/CA3 region of the hippocampus PubMed:28745240
Recent evidence has cogently shown that Amyloid-β induces apoptosis in rat primary neurons and human post-mitotic neuronal cells by reducing Bcl-XL expression level and evoking the release of cytochrome c from the mitochondria in a NF-κB – dependent manner PubMed:28745240
Preponderance of evidence has implicated NF-κB as a survival factor in neurons [24, 114, 115] primarily because of the ability of NF-κB to suppress apoptosis in response to excitotoxic and apoptotic stimuli PubMed:28745240
The anti-apoptotic effects of NF-κB have been ascribed to its ability to trans-activate the expression of a multitude of anti-apoptotic genes such as Bcl-2, Bcl-XL, and Bfl-1/A1 in the neurons of the amygdala, olfactory bulb, and the CA1/CA3 region of the hippocampus PubMed:28745240
The anti-apoptotic effects of NF-κB have been ascribed to its ability to trans-activate the expression of a multitude of anti-apoptotic genes such as Bcl-2, Bcl-XL, and Bfl-1/A1 in the neurons of the amygdala, olfactory bulb, and the CA1/CA3 region of the hippocampus PubMed:28745240
The anti-apoptotic effects of NF-κB have been ascribed to its ability to trans-activate the expression of a multitude of anti-apoptotic genes such as Bcl-2, Bcl-XL, and Bfl-1/A1 in the neurons of the amygdala, olfactory bulb, and the CA1/CA3 region of the hippocampus PubMed:28745240
NF-κB activity abrogates Amyloid-β peptide-induced toxicity in dissociated hippocampal cultures from C57Bl/6 mice PubMed:28745240
Multiple studies have implicated NF-κB in the regulation of post-natal axonal growth or neurite outgrowth. PubMed:28745240
NF-κB activation also protects hippocampal neurons from oxidative stress-induced apoptosis by inducing manganese superoxide dismutase (MnSOD) expression and mitigating peroxynitrite-induced protein nitration PubMed:28745240
Furthermore, Amyloid-β –induced NF-κB also results in the up-regulation of the antioxidant mitochondrial membrane enzyme – MnSOD (superoxide dismutase 2) [328] which is well known to combat oxidative stress and apoptosis PubMed:28745240
NF-κB activation also protects hippocampal neurons from oxidative stress-induced apoptosis by inducing manganese superoxide dismutase (MnSOD) expression and mitigating peroxynitrite-induced protein nitration PubMed:28745240
The trophic factors that evoke proliferation of NPC by inducing activation of NF-κB include epidermal growth factor (EGF) [155-161], basic fibroblast growth factor (bFGF) [155-161], vascular endothelial growth factor (VEGF) [162], tumor necrosis factor α (TNFα) [163], and erythropoietin (EPO) PubMed:28745240
Physiological, pathophysiological, and biochemical stimuli known to induce proliferation of NPC via NF-κB activation include cerebral infarction [165], traumatic brain injury [166], reactive oxygen species [167], hypoxia [168-172], sAPPα [147], and sphingosine-1-phosphate [173] PubMed:28745240
NF-κB also plays a vital role in axon guidance subsequent to neurogenesis and axon growth in response to neurotrophins, resulting in the integration of the nascent neurons PubMed:28745240
Moreover, NF-κB mediates the NSC migration in response to physiological and pathophysiological stimuli such as cerebral cortex injury [181], seizure [182], and ischemic stroke PubMed:28745240
Moreover, NF-κB mediates the NSC migration in response to physiological and pathophysiological stimuli such as cerebral cortex injury [181], seizure [182], and ischemic stroke PubMed:28745240
NF-κB also plays a pivotal role in the differentiation of neural stem cells PubMed:28745240
NF-κB positively regulates the transcription of interleukin 6 (IL6) family of cytokines such as IL6, leukemia inhibitory factor (LIF) and ciliary neurotrophic factor (CNTF) [184], which in-turn induce the differentiation of NSC into astrocytes by activating transcription factors STAT3, AP-1, and NF-κB itself PubMed:28745240
IL6 is another NF-κB – induced [256-260] pro-inflammatory cytokine up-regulated and integrally involved in the etio-pathogenesis of Alzheimer’s disease PubMed:28745240
Furthermore, NF-κB - induced IL6 has been demonstrated to evoke hyperphosphorylation of tau at Ser202 and Thr205 via the activation of the cdk5/p35 complex PubMed:28745240
Amyloid-β also induces microglial activation that results in NF-κB – induced expression of pro-inflammatory cytokines such as TNFα, IL1β, IL6, and IL8 from the microglia resulting in neuronal death PubMed:28745240
NF-κB positively regulates the transcription of interleukin 6 (IL6) family of cytokines such as IL6, leukemia inhibitory factor (LIF) and ciliary neurotrophic factor (CNTF) [184], which in-turn induce the differentiation of NSC into astrocytes by activating transcription factors STAT3, AP-1, and NF-κB itself PubMed:28745240
NF-κB positively regulates the transcription of interleukin 6 (IL6) family of cytokines such as IL6, leukemia inhibitory factor (LIF) and ciliary neurotrophic factor (CNTF) [184], which in-turn induce the differentiation of NSC into astrocytes by activating transcription factors STAT3, AP-1, and NF-κB itself PubMed:28745240
NF-κB positively regulates the transcription of interleukin 6 (IL6) family of cytokines such as IL6, leukemia inhibitory factor (LIF) and ciliary neurotrophic factor (CNTF) [184], which in-turn induce the differentiation of NSC into astrocytes by activating transcription factors STAT3, AP-1, and NF-κB itself PubMed:28745240
NF-κB is also indispensable in the neuronal differentiation of neuroblastoma cells [186] as its transcriptional activity directly orchestrates dendritic spine formation and neurite outgrowth PubMed:28745240
NF-κB is also indispensable in the neuronal differentiation of neuroblastoma cells [186] as its transcriptional activity directly orchestrates dendritic spine formation and neurite outgrowth PubMed:28745240
Multiple studies have implicated NF-κB in the regulation of post-natal axonal growth or neurite outgrowth. PubMed:28745240
Both, brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) promote neurite outgrowth, in a NF- κB - dependent manner, in primary cultures of nodose ganglion sensory neurons from developing mice PubMed:28745240
This paradoxical incongruity in the effects of NF-κB emanate from the prevailing phosphorylation status of the p65 subunit (Ser536) and coinciding physiological and biochemical stimuli, with the phosphorylation status of p65 being inversely related to the NF-κB – induced neurite outgrowth PubMed:28745240
NF-κB also plays a vital role in axon guidance subsequent to neurogenesis and axon growth in response to neurotrophins, resulting in the integration of the nascent neurons PubMed:28745240
NF-κB positively regulates the expression of extracellular matrix protein involved in cell adhesion, β1-integrin [199], a well characterized pivotal player in axon growth initiation and guidance PubMed:28745240
Furthermore, NF-κB directly regulates the expression of a plethora of cell adhesion molecules such as neural cell adhesion molecule (NCAM) [202], slit and Trk-like family member 1 (SLITRK1) [203], glial cell-derived neurotrophic factor receptor α1 (GFRα1) [204], and T-lymphoma and metastasis 1 (TLAM1) [203], key players in directing axon growth. PubMed:28745240
Furthermore, NF-κB directly regulates the expression of a plethora of cell adhesion molecules such as neural cell adhesion molecule (NCAM) [202], slit and Trk-like family member 1 (SLITRK1) [203], glial cell-derived neurotrophic factor receptor α1 (GFRα1) [204], and T-lymphoma and metastasis 1 (TLAM1) [203], key players in directing axon growth. PubMed:28745240
Furthermore, NF-κB directly regulates the expression of a plethora of cell adhesion molecules such as neural cell adhesion molecule (NCAM) [202], slit and Trk-like family member 1 (SLITRK1) [203], glial cell-derived neurotrophic factor receptor α1 (GFRα1) [204], and T-lymphoma and metastasis 1 (TLAM1) [203], key players in directing axon growth. PubMed:28745240
Furthermore, NF-κB directly regulates the expression of a plethora of cell adhesion molecules such as neural cell adhesion molecule (NCAM) [202], slit and Trk-like family member 1 (SLITRK1) [203], glial cell-derived neurotrophic factor receptor α1 (GFRα1) [204], and T-lymphoma and metastasis 1 (TLAM1) [203], key players in directing axon growth. PubMed:28745240
NF-κB is integrally involved in the orchestration of growth of dendritic arbors and critically regulates dendritic morphology because of its indispensable role in dendritic growth and branching PubMed:28745240
NF-κB is integrally involved in the orchestration of growth of dendritic arbors and critically regulates dendritic morphology because of its indispensable role in dendritic growth and branching PubMed:28745240
NF-κB activation directly induces the transcription of Hes1 and Hes5 [206, 207], two key transcription factors involved in the regulation of expression of proteins involved in dendritic growth, morphology, and branching PubMed:28745240
NF-κB activation directly induces the transcription of Hes1 and Hes5 [206, 207], two key transcription factors involved in the regulation of expression of proteins involved in dendritic growth, morphology, and branching PubMed:28745240
NF-κB activates the expression of the two microtubule-associated proteins, microtubule-associated protein 1B (MAP1B) and microtubule-associated protein 2 (MAP2) [209], two major proteins known to play a pivotal role in the growth, elongation, and arborization of dendrites PubMed:28745240
NF-κB activates the expression of the two microtubule-associated proteins, microtubule-associated protein 1B (MAP1B) and microtubule-associated protein 2 (MAP2) [209], two major proteins known to play a pivotal role in the growth, elongation, and arborization of dendrites PubMed:28745240
NF-κB directly regulates the transcription of a multitude of proteins of the complement pathway that are involved in antigen presenting such as C3 (complement component 3) [241], Bf (complement factor B) [242], and CR2 (complement receptor 2) [243] as well as acute phase proteins such as C4 (complement factor 4) [244] and C4BPA (complement factor 4 binding protein) PubMed:28745240
NF-κB directly regulates the transcription of a multitude of proteins of the complement pathway that are involved in antigen presenting such as C3 (complement component 3) [241], Bf (complement factor B) [242], and CR2 (complement receptor 2) [243] as well as acute phase proteins such as C4 (complement factor 4) [244] and C4BPA (complement factor 4 binding protein) PubMed:28745240
NF-κB directly regulates the transcription of a multitude of proteins of the complement pathway that are involved in antigen presenting such as C3 (complement component 3) [241], Bf (complement factor B) [242], and CR2 (complement receptor 2) [243] as well as acute phase proteins such as C4 (complement factor 4) [244] and C4BPA (complement factor 4 binding protein) PubMed:28745240
NF-κB directly regulates the transcription of a multitude of proteins of the complement pathway that are involved in antigen presenting such as C3 (complement component 3) [241], Bf (complement factor B) [242], and CR2 (complement receptor 2) [243] as well as acute phase proteins such as C4 (complement factor 4) [244] and C4BPA (complement factor 4 binding protein) PubMed:28745240
NF-κB directly regulates the transcription of a multitude of proteins of the complement pathway that are involved in antigen presenting such as C3 (complement component 3) [241], Bf (complement factor B) [242], and CR2 (complement receptor 2) [243] as well as acute phase proteins such as C4 (complement factor 4) [244] and C4BPA (complement factor 4 binding protein) PubMed:28745240
It is well established that NF-κB is one of the most prominent transcription factors that regulates IL1β production PubMed:28745240
Amyloid-β also induces microglial activation that results in NF-κB – induced expression of pro-inflammatory cytokines such as TNFα, IL1β, IL6, and IL8 from the microglia resulting in neuronal death PubMed:28745240
Moreover, NF-κB – induced IL1 genesis has been shown to precipitate tau phosphorylation at Ser202 and Thr205 (AT8 epitopes) via the activation of the p38- MAPK pathway PubMed:28745240
Moreover, NF-κB – induced IL1 genesis has been shown to precipitate tau phosphorylation at Ser202 and Thr205 (AT8 epitopes) via the activation of the p38- MAPK pathway PubMed:28745240
Furthermore, NF-κB - induced IL6 has been demonstrated to evoke hyperphosphorylation of tau at Ser202 and Thr205 via the activation of the cdk5/p35 complex PubMed:28745240
Furthermore, NF-κB - induced IL6 has been demonstrated to evoke hyperphosphorylation of tau at Ser202 and Thr205 via the activation of the cdk5/p35 complex PubMed:28745240
Another known target of NF-κB, TNFα [266, 267] is also up-regulated in the cortex [268], cerebrospinal fluid, and the serum of Alzheimer’s disease patients PubMed:28745240
Furthermore, Amyloid-β actuates NF-κB – dependent pro-inflammatory pathways in microglia culminating in TNFα expression and subsequently TNFα effectuated neurotoxicity PubMed:28745240
Amyloid-β also induces microglial activation that results in NF-κB – induced expression of pro-inflammatory cytokines such as TNFα, IL1β, IL6, and IL8 from the microglia resulting in neuronal death PubMed:28745240
Multiple studies have cogently shown that the inhibition of NF-κB activity results in the mitigation of secreted Amyloid-β by cultured cells in vitro PubMed:28745240
NF-κB is also widely implicated in the engenderment of Amyloid-β in vivo in a multitude of mouse models PubMed:28745240
A multitude of studies have demonstrated that NF-κB directly regulates the transcription and expression of BACE1, thereby eliciting profound effects on AβPP processing and engenderment of Amyloid-β PubMed:28745240
Indeed, Checler and colleagues have shown in a recent study that, NF-κB mediates the Amyloid-β – induced increase in expression of AβPP in HEK293 cells PubMed:28745240
A multitude of studies have demonstrated that NF-κB directly regulates the transcription and expression of BACE1, thereby eliciting profound effects on AβPP processing and engenderment of Amyloid-β PubMed:28745240
NF-κB induced up-regulation in BACE1 expression is contingent on the nature of the NF-κB heterodimer PubMed:28745240
A multitude of studies have demonstrated that NF-κB directly regulates the transcription and expression of BACE1, thereby eliciting profound effects on AβPP processing and engenderment of Amyloid-β PubMed:28745240
Recent studies have unveiled a novel role of NF-κB in the regulation of the γ-secretase activity mediated processing of the C99 (CTFβ) fragment PubMed:28745240
Recent studies have unveiled a novel role of NF-κB in the regulation of the γ-secretase activity mediated processing of the C99 (CTFβ) fragment PubMed:28745240
In addition to augmenting γ-secretase activity, NF-κB also regulates the expression of the PS1 subunit of the γ-secretase complex PubMed:28745240
In addition to augmenting γ-secretase activity, NF-κB also regulates the expression of the PS1 subunit of the γ-secretase complex PubMed:28745240
Furthermore, two κB-binding sites have been identified in the proximal promoter region of AβPP, suggesting the potential regulation of AβPP expression by NF-κB PubMed:28745240
Indeed, Checler and colleagues have shown in a recent study that, NF-κB mediates the Amyloid-β – induced increase in expression of AβPP in HEK293 cells PubMed:28745240
The three well characterized sensors of intracellular calcium – calmodulin/CamKII pathway, PI3K/ Akt pathway, and protein kinase C (PKC) pathway – are known to induce NF-κB activation and couple upstream signal transduction pathways that induce calcium dyshomeostasis to NF-κB activation PubMed:28745240
Amyloid-β also induces microglial activation that results in NF-κB – induced expression of pro-inflammatory cytokines such as TNFα, IL1β, IL6, and IL8 from the microglia resulting in neuronal death PubMed:28745240
In conditional neuronal NF-κB-deficient mice, loss of NF-κB signaling impaired synaptic transmission, spatial memory formation, and plasticity PubMed:25652642
In conditional neuronal NF-κB-deficient mice, loss of NF-κB signaling impaired synaptic transmission, spatial memory formation, and plasticity PubMed:25652642
In conditional neuronal NF-κB-deficient mice, loss of NF-κB signaling impaired synaptic transmission, spatial memory formation, and plasticity PubMed:25652642
Complete abrogation of the DNA binding ability of NFκB factors induces apoptosis of the neuronal cells PubMed:25652642
In primary neuronal cells, exposure to Aβ25-35 peptide increase NF-κB mediated transactivation of manganese superoxide dismutase (Mn-SOD), suppress peroxinitrite production and inhibit membrane depolarization, thereby preventing apoptosis induced by oxidative stress PubMed:25652642
Cell death is preceded by reduction in the NF-κB regulated transcription of anti-apoptotic genes suggesting that a minimal threshold of NF-κB activity is needed for neuronal survival PubMed:25652642
Various endogenous and exogenous stimuli activate NF-κB enhancing transactivation of inflammatory molecules and production of free radicals in glial cells PubMed:25652642
Various endogenous and exogenous stimuli activate NF-κB enhancing transactivation of inflammatory molecules and production of free radicals in glial cells PubMed:25652642
A consequence of intracellular and parenchymal accumulation of NPs and NFTs is activation of NF-κB in the neural and glial cells with subsequent protective or detrimental effects PubMed:25652642
A consequence of intracellular and parenchymal accumulation of NPs and NFTs is activation of NF-κB in the neural and glial cells with subsequent protective or detrimental effects PubMed:25652642
Increased presence of activated glial cells presenting elevated NF-κB and HLA-DR expression are commonly observed around the Aβ plaques in postmortem AD tissue PubMed:25652642
In neuronal cells Aβ1-42 peptide has been shown to regulate APP and BACE1 proteins in NF-κB dependent manner PubMed:25652642
In neuronal cells Aβ1-42 peptide has been shown to regulate APP and BACE1 proteins in NF-κB dependent manner PubMed:25652642
Under physiological conditions activation of NF-κB by endogenous Aβ reduces βAPP, BACE1 and the γ-secretase activity, thereby lowering Aβ processing and facilitating Aβ homeostasis PubMed:25652642
Under physiological conditions activation of NF-κB by endogenous Aβ reduces βAPP, BACE1 and the γ-secretase activity, thereby lowering Aβ processing and facilitating Aβ homeostasis PubMed:25652642
However in AD, exposure to high Aβ concentrations upregulates NF-κB activation increasing βAPP and Aβ processing, precipitating a feed-back loop that favor exacerbated Aβ production PubMed:25652642
Under physiological conditions activation of NF-κB by endogenous Aβ reduces βAPP, BACE1 and the γ-secretase activity, thereby lowering Aβ processing and facilitating Aβ homeostasis PubMed:25652642
However in AD, exposure to high Aβ concentrations upregulates NF-κB activation increasing βAPP and Aβ processing, precipitating a feed-back loop that favor exacerbated Aβ production PubMed:25652642
Under physiological conditions activation of NF-κB by endogenous Aβ reduces βAPP, BACE1 and the γ-secretase activity, thereby lowering Aβ processing and facilitating Aβ homeostasis PubMed:25652642
However in AD, exposure to high Aβ concentrations upregulates NF-κB activation increasing βAPP and Aβ processing, precipitating a feed-back loop that favor exacerbated Aβ production PubMed:25652642
Aβ has been shown to upregulate APOE in astroglial cells. This upregulation was inhibited by decoy-κB nucleotides supporting a critical role for NFκB in APOE function PubMed:25652642
Decoy κB nucleotides mediate cell death by blocking neurotrophins and anti-apoptotic factors supporting an essential role for NF-κB in the neuroprotective process PubMed:25652642
These NF-κB mediated neuroprotective effects have been largely observed in early stages of neuronal regeneration in AD PubMed:25652642
In primary neuronal cells, exposure to Aβ25-35 peptide increase NF-κB mediated transactivation of manganese superoxide dismutase (Mn-SOD), suppress peroxinitrite production and inhibit membrane depolarization, thereby preventing apoptosis induced by oxidative stress PubMed:25652642
In primary neuronal cells, exposure to Aβ25-35 peptide increase NF-κB mediated transactivation of manganese superoxide dismutase (Mn-SOD), suppress peroxinitrite production and inhibit membrane depolarization, thereby preventing apoptosis induced by oxidative stress PubMed:25652642
In primary neuronal cells, exposure to Aβ25-35 peptide increase NF-κB mediated transactivation of manganese superoxide dismutase (Mn-SOD), suppress peroxinitrite production and inhibit membrane depolarization, thereby preventing apoptosis induced by oxidative stress PubMed:25652642
Comparison of the cellular distribution of NF-κB in the nucleus basalis of Meynert of AD and control patients showed that the proportion of large cholinergic neurons with elevated nuclear p65 was significantly increased in AD, suggesting an association between NF–κB functions and the process of cholinergic degeneration PubMed:25652642
These observations substantiate a direct role of neuronal NF–κB activation in the pathogenesis of AD PubMed:25652642
Increased presence of activated glial cells presenting elevated NF-κB and HLA-DR expression are commonly observed around the Aβ plaques in postmortem AD tissue PubMed:25652642
Increased presence of NF-κB mediated IL-1β, IL-6, and TNF-α cytokines have been reported in the affected tissues, serum and CSF of AD patients PubMed:25652642
Excessive accumulation of Aβ1-42 stimulates microglial cells by signaling via receptor associated advanced glycation end products (RAGE) and peroxisome proliferator-activated receptor-γ (PPAR-γ), phosphorylates IKK proteins, and enhances NF-κB mediated transactivation of inflammatory cytokines and neurotoxic molecules such as glutamate and reactive oxygen species (ROS)/induced nitric oxide synthase (iNOS) [12] (Fig 2B) PubMed:25652642
Excessive accumulation of Aβ1-42 stimulates microglial cells by signaling via receptor associated advanced glycation end products (RAGE) and peroxisome proliferator-activated receptor-γ (PPAR-γ), phosphorylates IKK proteins, and enhances NF-κB mediated transactivation of inflammatory cytokines and neurotoxic molecules such as glutamate and reactive oxygen species (ROS)/induced nitric oxide synthase (iNOS) [12] (Fig 2B) PubMed:25652642
Excessive accumulation of Aβ1-42 stimulates microglial cells by signaling via receptor associated advanced glycation end products (RAGE) and peroxisome proliferator-activated receptor-γ (PPAR-γ), phosphorylates IKK proteins, and enhances NF-κB mediated transactivation of inflammatory cytokines and neurotoxic molecules such as glutamate and reactive oxygen species (ROS)/induced nitric oxide synthase (iNOS) [12] (Fig 2B) PubMed:25652642
Excessive accumulation of Aβ1-42 stimulates microglial cells by signaling via receptor associated advanced glycation end products (RAGE) and peroxisome proliferator-activated receptor-γ (PPAR-γ), phosphorylates IKK proteins, and enhances NF-κB mediated transactivation of inflammatory cytokines and neurotoxic molecules such as glutamate and reactive oxygen species (ROS)/induced nitric oxide synthase (iNOS) [12] (Fig 2B) PubMed:25652642
Furthermore NF-κB specific inhibitor prevents iNOS and ROS upregulation in Aβ stimulated cultures of astrocytes or mixed cortical cells PubMed:25652642
Excessive accumulation of Aβ1-42 stimulates microglial cells by signaling via receptor associated advanced glycation end products (RAGE) and peroxisome proliferator-activated receptor-γ (PPAR-γ), phosphorylates IKK proteins, and enhances NF-κB mediated transactivation of inflammatory cytokines and neurotoxic molecules such as glutamate and reactive oxygen species (ROS)/induced nitric oxide synthase (iNOS) [12] (Fig 2B) PubMed:25652642
Furthermore NF-κB specific inhibitor prevents iNOS and ROS upregulation in Aβ stimulated cultures of astrocytes or mixed cortical cells PubMed:25652642
Increased presence of NF-κB mediated IL-1β, IL-6, and TNF-α cytokines have been reported in the affected tissues, serum and CSF of AD patients PubMed:25652642
Increased presence of NF-κB mediated IL-1β, IL-6, and TNF-α cytokines have been reported in the affected tissues, serum and CSF of AD patients PubMed:25652642
Increased presence of NF-κB mediated IL-1β, IL-6, and TNF-α cytokines have been reported in the affected tissues, serum and CSF of AD patients PubMed:25652642
This is supported by the observation that in mixed neuronal-glial cell cultures, Aβ induces increasing degree of neurotoxicity in an NF-κB dependent manner in the presence of higher proportion of glial cells PubMed:25652642
Upregulation of several NF-κB regulated miRNAs such as miRNA-9, miRNA-34a, miRNA-125b, miRNA-146a, miRNA-155 and miRNA-339 5p have been observed in stressed primary human neuronalglial cells and in postmortem AD brain tissues PubMed:25652642
Upregulation of several NF-κB regulated miRNAs such as miRNA-9, miRNA-34a, miRNA-125b, miRNA-146a, miRNA-155 and miRNA-339 5p have been observed in stressed primary human neuronalglial cells and in postmortem AD brain tissues PubMed:25652642
Upregulation of several NF-κB regulated miRNAs such as miRNA-9, miRNA-34a, miRNA-125b, miRNA-146a, miRNA-155 and miRNA-339 5p have been observed in stressed primary human neuronalglial cells and in postmortem AD brain tissues PubMed:25652642
Upregulation of several NF-κB regulated miRNAs such as miRNA-9, miRNA-34a, miRNA-125b, miRNA-146a, miRNA-155 and miRNA-339 5p have been observed in stressed primary human neuronalglial cells and in postmortem AD brain tissues PubMed:25652642
Upregulation of several NF-κB regulated miRNAs such as miRNA-9, miRNA-34a, miRNA-125b, miRNA-146a, miRNA-155 and miRNA-339 5p have been observed in stressed primary human neuronalglial cells and in postmortem AD brain tissues PubMed:25652642
Upregulation of several NF-κB regulated miRNAs such as miRNA-9, miRNA-34a, miRNA-125b, miRNA-146a, miRNA-155 and miRNA-339 5p have been observed in stressed primary human neuronalglial cells and in postmortem AD brain tissues PubMed:25652642
BEL Commons is developed and maintained in an academic capacity by Charles Tapley Hoyt and Daniel Domingo-Fernández at the Fraunhofer SCAI Department of Bioinformatics with support from the IMI project, AETIONOMY. It is built on top of PyBEL, an open source project. Please feel free to contact us here to give us feedback or report any issues. Also, see our Publishing Notes and Data Protection information.
If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.