a(CHEBI:"amyloid-beta polypeptide 42")
Despite enhanced Aβ42 accumulation in AD brain (Lewczuk et al. 2003), concentrations of monomeric Aβ42 in the CSF of AD patients are decreased PubMed:29196815
Other endogenous ligands that impact on the activity of nAChRs noncompetitively and voltage independently include the amyloid beta peptide 1-42 (Abeta1-42; Refs. 123, 376) and the canabinoid anandamide (356, 442). PubMed:19126755
The Abeta1-42 peptide is one of the breakdown products of the proteolytic cleavage of the amyloid precursor protein by beta- and gamma-secretases. In biopsy samples of human brain tissue obtained from AD patients and in ectopic systems overexpressing either alpha7 nAChRs or APP, Abeta1-42 coimmunoprecipitates with alpha7 nAChRs (490). The Abeta1-42 peptide also displaces binding of [3H]MLA from alpha7 nAChRs in cerebral cortical and hippocampal synaptosomes (490). PubMed:19126755
The Abeta1-42 peptide is one of the breakdown products of the proteolytic cleavage of the amyloid precursor protein by beta- and gamma-secretases. In biopsy samples of human brain tissue obtained from AD patients and in ectopic systems overexpressing either alpha7 nAChRs or APP, Abeta1-42 coimmunoprecipitates with alpha7 nAChRs (490). The Abeta1-42 peptide also displaces binding of [3H]MLA from alpha7 nAChRs in cerebral cortical and hippocampal synaptosomes (490). PubMed:19126755
An increasing ratio of the full-length, 1–42 peptide to the 1–40 form is associated with disease (Kumar-Singh et al., 2006), and mutations underlying familial forms of AD either increase this ratio or increase the amount of Abeta secreted. PubMed:19293145
Moreover, the M1 agonist AF267B can rescue the cognitive impairment and decrease Aβ42 and tau abnormalities in the cortex and hippocampus of a mouse model of AD PubMed:26813123
Administration of AF267B and AF102B (Cevimeline, EVOXACTM), an M1 mAChRselective agonist once prescribed for the treatment of Sjogren’s syndrome, decreases Abeta42 levels in the cerebral spinal fluid (CSF) of rabbits without affecting APP PubMed:24590577
Administration of AF267B and AF102B (Cevimeline, EVOXACTM), an M1 mAChRselective agonist once prescribed for the treatment of Sjogren’s syndrome, decreases Abeta42 levels in the cerebral spinal fluid (CSF) of rabbits without affecting APP PubMed:24590577
The analysis of the Abeta fraction reduced by nicotine showed that mainly insoluble Ab1-40/42 was affected while there was no change in soluble Abeta (Nordberg et al., 2002) PubMed:25514383
The short-term treatment of 10 days showed a significant reduction in cortical insoluble Abeta1-40/42 PubMed:25514383
When a higher dose of pioglitazone (7 days/40 mg/kg/day) was used in 10-monthold transgenic mice overexpressing the APP V717I mutation, a 20-- 25% decrease in plaque burden was observed with significant reduction in Ab42 levels within the brains of these animals [61]. PubMed:21718217
Pedersen and Flynn examined the effects of rosiglitazone and found that activation of PPAR-g ameliorated behavioral deficits in the Tg2576 AD mouse model. However, these animals displayed no changes in plaque pathology, but had reduced brain Ab42 levels. PubMed:21718217
The Ab peptide is generated by the sequential cleavage of the amyloid precursor protein (APP) by the b and g secretases, resulting in the generation of peptides 40 or 42 amino acids in length [2]. PubMed:21718217
Recently, a novel group of M1 partial agonists was developed (AF102B, AF150(S) and AF267B-i) [129]. In a series of studies using the 3x transgenic-AD mice, which recapitulate the major pathologies of AD [130], chronic AF267B treatment rescued cognitive impairment and decreased Abeta42 and tau pathologies in the cortex and hippocampus. These changes were associated with M1 mAChR-mediated activation of the TNFalpha-converting enzyme ADAM17/TACE, decreased BACE1 steady state levels and inhibition of GSK3beta [130]. PubMed:18986241
As with nicotine, the weak alpha7 nAChR agonist GTS-21 is neuroprotective, specifically protecting against Abeta1–42-elicited neurotoxicity154. This effect is probably due to small, protracted increases in receptor-mediated Ca2+ influx. importantly, high concentrations of GTS-21 reduced cell survival, underlining the possible risk of over-stimulation152 PubMed:19721446
This functional screen identified 18 genes (Figure 3D), corresponding to ten ATP-dependent chaperones, HSC70 (hsp-1), HSP90 (daf-21), and eight subunits of the CCT/TRiC chaperonin complex; the co-chaperones, HSP40 (dnj-12) and CDC37 (cdc-37); and the TPR-domain pro- tein STI1 that upon knockdown significantly enhanced A b 42 pro- teotoxicity (Figure 3D). PubMed:25437566
This functional screen identified 18 genes (Figure 3D), corresponding to ten ATP-dependent chaperones, HSC70 (hsp-1), HSP90 (daf-21), and eight subunits of the CCT/TRiC chaperonin complex; the co-chaperones, HSP40 (dnj-12) and CDC37 (cdc-37); and the TPR-domain pro- tein STI1 that upon knockdown significantly enhanced A b 42 pro- teotoxicity (Figure 3D). PubMed:25437566
This functional screen identified 18 genes (Figure 3D), corresponding to ten ATP-dependent chaperones, HSC70 (hsp-1), HSP90 (daf-21), and eight subunits of the CCT/TRiC chaperonin complex; the co-chaperones, HSP40 (dnj-12) and CDC37 (cdc-37); and the TPR-domain pro- tein STI1 that upon knockdown significantly enhanced A b 42 pro- teotoxicity (Figure 3D). PubMed:25437566
This functional screen identified 18 genes (Figure 3D), corresponding to ten ATP-dependent chaperones, HSC70 (hsp-1), HSP90 (daf-21), and eight subunits of the CCT/TRiC chaperonin complex; the co-chaperones, HSP40 (dnj-12) and CDC37 (cdc-37); and the TPR-domain pro- tein STI1 that upon knockdown significantly enhanced A b 42 pro- teotoxicity (Figure 3D). PubMed:25437566
This functional screen identified 18 genes (Figure 3D), corresponding to ten ATP-dependent chaperones, HSC70 (hsp-1), HSP90 (daf-21), and eight subunits of the CCT/TRiC chaperonin complex; the co-chaperones, HSP40 (dnj-12) and CDC37 (cdc-37); and the TPR-domain pro- tein STI1 that upon knockdown significantly enhanced A b 42 pro- teotoxicity (Figure 3D). PubMed:25437566
Indeed, clioquinol countered disruption of autophagy by chloroquine in retinal cells, reduced Aβ42 accumulation in CHO cells expressing APP and mutant presenilin 1 and diminished amyloid misfolding and aggregation in Tg2576 AD mice 196,197 . PubMed:30116051
Cilostazol (a phosphodiesterase 3 inhibitor) clears Aβ42 from neuronal cell lines by promoting autophagy, upregulating beclin 1, ATG5 and LC3, downregulating mTORC1 and inducing lysosomal cathepsin B; these actions of cilostazol involve activation of SIRT1 as well as upstream Tyr172 phosphorylation of AMPK 108,162,163 . PubMed:30116051
Cilostazol improved cognition and reduced levels of Aβ42 and hyperphosphorylated tau following intra- cerebroventricular injection of Aβ25–35 into mice 162,163 . PubMed:30116051
Interestingly, resver- atrol downregulated RAGE as well as MMP9 — an effect that is related to decreased hippocampal load of Aβ42 (REF.297) . PubMed:30116051
The antibiotic rifampicin likewise promoted Aβ42 clearance by induc- ing BBB-localized LRP1 and P glycoprotein 1 (REFS273,292) . PubMed:30116051
Third, apolipoprotein E allele 4 (APOE4), a major risk allele for sporadic AD, is associated with increased generation and accumula- tion of Aβ42 (REFS59,60) . PubMed:30116051
Tau, α-synuclein and TDP43 are substrates for CMA degradation, as are amyloid precursor protein (APP) but not amyloid-β fragment 42 (Aβ42) itself 3,45–47,48 . PubMed:30116051
Similar to IDE, neprilysin catabolizes Aβ42, and its loss in mouse models of AD and in patients with AD alike also contributes to Aβ42 accumulation 253,256,260 . PubMed:30116051
Like IDE and neprilysin, plasmin degrades Aβ42 and blocks Aβ42-induced toxicity, suggesting that the decrease in its levels in AD is involved in the evolution of AD 254,256,261 . PubMed:30116051
Compared with control neurons, the effects of Ab42 on tau phosphorylation at CP13, PHF-1 and AT180 epitopes were significantly ameliorated in AK1 knockdown cortical neurons PubMed:22419736
As shown in Figure 5A and B, treatment of control cells with Ab42 reduced the levels of AMPK phosphorylation at Thr172 and the inhibitory phosphorylation of GSK3b at Ser9. On the contrary, these alterations triggered by Ab42 were not observed in SH-SY5Y/AK1 knockdown cells, showing no changes in the levels of the phosphorylated AMPK and GSK3b. These results suggest that AK1 plays a crucial role in the regulation of AMPK and GSK3b in the neuronal cells exposed to Ab42. PubMed:22419736
A number of studies have found that Ab species, including oligomeric Ab42, are important factors responsible for tau pathogenesis PubMed:22419736
Given the size of AD-related proteins, mono- meric Aβ1-40, Aβ1-42 and tau, should be able to pass freely through astrocytic endfeet clefts at the glial barrier.72 PubMed:26195256
By measuring Aβ levels in superior vena cava and inferior vena cava, it is clear thatAβ levels are getting lower and lower along the direction of the vein blood flow, and the contents of Aβ40 and total Aβ in artery are significantly less than those in vein, suggesting a part of Aβ40 and total Aβ can be cleared by peripheral organs and tissues, such as the liver, kidney, skin, and the gastrointestinal tract, although there is no change in Aβ42 concentrations (Xiang et al. 2015) PubMed:29626319
By measuring Aβ levels in superior vena cava and inferior vena cava, it is clear thatAβ levels are getting lower and lower along the direction of the vein blood flow, and the contents of Aβ40 and total Aβ in artery are significantly less than those in vein, suggesting a part of Aβ40 and total Aβ can be cleared by peripheral organs and tissues, such as the liver, kidney, skin, and the gastrointestinal tract, although there is no change in Aβ42 concentrations (Xiang et al. 2015) PubMed:29626319
By measuring Aβ levels in superior vena cava and inferior vena cava, it is clear thatAβ levels are getting lower and lower along the direction of the vein blood flow, and the contents of Aβ40 and total Aβ in artery are significantly less than those in vein, suggesting a part of Aβ40 and total Aβ can be cleared by peripheral organs and tissues, such as the liver, kidney, skin, and the gastrointestinal tract, although there is no change in Aβ42 concentrations (Xiang et al. 2015) PubMed:29626319
By measuring Aβ levels in superior vena cava and inferior vena cava, it is clear thatAβ levels are getting lower and lower along the direction of the vein blood flow, and the contents of Aβ40 and total Aβ in artery are significantly less than those in vein, suggesting a part of Aβ40 and total Aβ can be cleared by peripheral organs and tissues, such as the liver, kidney, skin, and the gastrointestinal tract, although there is no change in Aβ42 concentrations (Xiang et al. 2015) PubMed:29626319
In addition, Aβ1–42 can increase the expression of TREM2, a surface signaling receptor in microglia, and the up-regulation of TRME2 can facilitate microglial phagocytosis of Aβ1–42 PubMed:29626319
In addition, Aβ1–42 can increase the expression of TREM2, a surface signaling receptor in microglia, and the up-regulation of TRME2 can facilitate microglial phagocytosis of Aβ1–42 PubMed:29626319
Recently, Kaushal et al. described the involvement of NLRP1 inflammasome activation in neurons. In these experiments, serum deprivation induced NLRP1-dependent caspase-1 activity and ASC speck formation, which resulted in caspase-6 activation and an increase in the Ab42/total Ab ratio (11) PubMed:28019679
Anatabine dose dependently inhibited Aβ1–40 and Aβ1–42 with an approximate half maximal inhibitory concentration of 640 μg/ml for both Aβ1–40 and Aβ1–42 (Fig. 2). PubMed:21958873
We then tested the impact of anatabine on sAPPα and sAPPβ production using 7W CHO cells and observed that anatabine inhibits sAPPβ secretion without impacting sAPPα suggesting that anatabine is preventing the β-cleavage of APP (Fig. 4). PubMed:21958873
A significant reduction in the accumulation of brain soluble and insoluble Aβ1–40 and Aβ1–42 was observed following four days of treatment with 2 mg/kg of anatabine (Fig. 9). PubMed:21958873
Consistent with these findings, strong overexpression of human Ab42, but not Ab40, in Drosophila neurons induces age-related accumulation of Ab in autolysosomes and neurotoxicity (Ling et al. 2009). PubMed:22908190
By up-regulating endocytosis, high dietary LDL-cholesterol and overexpression of its receptor ApoE (particularly ApoE 14) elevate bCTF levels and increase delivery of Ab1–42 to lysosomes in cellular model systems (Ji et al. 2006; Cossec et al. 2010). PubMed:22908190
By up-regulating endocytosis, high dietary LDL-cholesterol and overexpression of its receptor ApoE (particularly ApoE 14) elevate bCTF levels and increase delivery of Ab1–42 to lysosomes in cellular model systems (Ji et al. 2006; Cossec et al. 2010). PubMed:22908190
By up-regulating endocytosis, high dietary LDL-cholesterol and overexpression of its receptor ApoE (particularly ApoE 14) elevate bCTF levels and increase delivery of Ab1–42 to lysosomes in cellular model systems (Ji et al. 2006; Cossec et al. 2010). PubMed:22908190
Consistent with these findings, strong overexpression of human Ab42, but not Ab40, in Drosophila neurons induces age-related accumulation of Ab in autolysosomes and neurotoxicity (Ling et al. 2009). PubMed:22908190
We observed that BAY61-3606 significantly reduces brain Aβ38, Aβ40, and Aβ42 levels in Tg PS1/ APPsw mice (Fig. 7, C and D). PubMed:25331948
In addition, we found that BAY61-3606 stimulates the clearance of Aβ across the BBB in wild-type mice as demonstrated by increased circulating plasma levels of human Aβ42 in mice treated with the Syk inhibitor compared with vehicle-treated mice following the intracranial injection of human Aβ42 (Fig. 7B) PubMed:25331948
We found that both the (-)- and (+)-nilvadipine enantiomers enhance Aβ42 clearance from the brain to the peripheral side of the in vitro BBB model (Fig. 2A). PubMed:25331948
Data show that (-)-nilvadipine stimulated the clearance of human Aβ42 across the BBB as more human Aβ42 was detected in the plasma of (-)-nilvadipine-treated mice than control animals (Fig. 2B). PubMed:25331948
Moreover, the level of A 1-42 was lowered by L-theanine and caused A 1-42- activated neuronal cell death in the cortex and hip-pocampus of the brain [128]. PubMed:29179999
It con-siderably lowered the expression of A 1-40 and A 1-42 in an AD transgenic mouse [195]. PubMed:29179999
LPS-stimulated memory impairments were improved by 4-O-methylhonokinol through the inhibition of A 1-42 expression. PubMed:29179999
ICV infusion of impairments by A 1-42 was considerably reduced with the treatment of obovatol [161]. PubMed:29179999
Nicorandil, ATP-sensitive potassium channel opener, reduced apo- ptosis and decreased oxidative stress, downregulated APP695 mRNA and APP695 protein expression, also reduced Aβ 42 levels in the medium [90]. PubMed:27288790
L-Theanine, an amino acid in green tea, reduced Aβ 42 levels in the cortex and hippocampus of the brain, which is mediated by suppres- sion of ERK/p38 and NF-κB as well as the reduction of macromolecular oxidative damage [81]. PubMed:27288790
Upon exposure to various cell stressors including Aβ 42 , expression of BACE1-AS becomes elevated, increasing BACE1 mRNA stability and generating additional Aβ 42 through a post-transcriptional feed-forward mechanism [74]. PubMed:27288790
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
Despite enhanced Aβ42 accumulation in AD brain (Lewczuk et al. 2003), concentrations of monomeric Aβ42 in the CSF of AD patients are decreased PubMed:29196815
Other studies have reported that alpha4beta2 nAChRs are more sensitive than alpha7 nAChRs to inhibition by nanomolar concentrations of Abeta1-42 (506). PubMed:19126755
Other endogenous ligands that impact on the activity of nAChRs noncompetitively and voltage independently include the amyloid beta peptide 1-42 (Abeta1-42; Refs. 123, 376) and the canabinoid anandamide (356, 442). PubMed:19126755
It is noteworthy that the alpha7 nAChR activity increases intracellular accumulation of Abeta in neurons (336), and Abeta peptides, in addition to modulating nAChR activity, downregulate the expression of nAChRs (197). PubMed:19126755
The Abeta1-42 peptide is one of the breakdown products of the proteolytic cleavage of the amyloid precursor protein by beta- and gamma-secretases. In biopsy samples of human brain tissue obtained from AD patients and in ectopic systems overexpressing either alpha7 nAChRs or APP, Abeta1-42 coimmunoprecipitates with alpha7 nAChRs (490). The Abeta1-42 peptide also displaces binding of [3H]MLA from alpha7 nAChRs in cerebral cortical and hippocampal synaptosomes (490). PubMed:19126755
The Abeta1-42 peptide is one of the breakdown products of the proteolytic cleavage of the amyloid precursor protein by beta- and gamma-secretases. In biopsy samples of human brain tissue obtained from AD patients and in ectopic systems overexpressing either alpha7 nAChRs or APP, Abeta1-42 coimmunoprecipitates with alpha7 nAChRs (490). The Abeta1-42 peptide also displaces binding of [3H]MLA from alpha7 nAChRs in cerebral cortical and hippocampal synaptosomes (490). PubMed:19126755
More functional studies reported that while at picomolar concentrations Abeta1-42 activates alpha7 nAChRs ectopically expressed in Xenopus oocytes (123, 126), at nanomolar concentrations it inhibits alpha7 nAChRs present in different preparations (278, 376). The alpha7 nAChR inhibition by Abeta1-42 is noncompetitive with respect to the agonist, is voltage independent, and is therefore likely to be mediated by the interaction of the peptide with a site different from that for ACh on the nAChRs. PubMed:19126755
It is noteworthy that the alpha7 nAChR activity increases intracellular accumulation of Abeta in neurons (336), and Abeta peptides, in addition to modulating nAChR activity, downregulate the expression of nAChRs (197). PubMed:19126755
An increasing ratio of the full-length, 1–42 peptide to the 1–40 form is associated with disease (Kumar-Singh et al., 2006), and mutations underlying familial forms of AD either increase this ratio or increase the amount of Abeta secreted. PubMed:19293145
Abeta1–42 activates heterologously expressed nAChRs (Dineley et al., 2002), and Abeta25–35 has been shown to activate non-alpha7 nAChRs in rat basal forebrain neurons (Fu and Jhamandas, 2003) and to evoke a alpha7- mediated calcium increases in presynaptic terminals isolated from rat hippocampus and neocortex (Dougherty et al., 2003). PubMed:19293145
With the use of selective antagonists it was possible to determine that inhibition operates on both alpha7 and non-alpha7 receptors (Pettit et al., 2001) PubMed:25514383
Modulation of nAChRs by Abeta was also found in ex vivo studies: Pettit and colleagues (2001) used rat hippocampal slices to show that Abeta1-42 incubation is able to reduce postsynaptic currents and open probability of both alpha7 and non-alpha7 nAChRs subtypes, demonstrating an interaction between Abeta and other nAChR subunits PubMed:25514383
They demonstrated that Abeta1-42 drives a reversible inhibition of nAChR-mediated currents in hippocampal GABAergic neurons recorded from rat slices. In these experimental conditions the most effective Abeta1-42 concentration was 500 nM, but inhibition was found also at the lower concentration of 100 nM PubMed:25514383
They demonstrated that Abeta1-42 drives a reversible inhibition of nAChR-mediated currents in hippocampal GABAergic neurons recorded from rat slices. In these experimental conditions the most effective Abeta1-42 concentration was 500 nM, but inhibition was found also at the lower concentration of 100 nM PubMed:25514383
With the use of selective antagonists it was possible to determine that inhibition operates on both alpha7 and non-alpha7 receptors (Pettit et al., 2001) PubMed:25514383
The incubation of cultured rat hippocampal neurons with Abeta1-42 resulted in inhibition of alpha7 nAChRs, more precisely of both somato-dendritic and presynaptic populations of receptors PubMed:25514383
Further studies showed an inhibitory effect of Abeta1-42 on human alpha4beta2 nAChRs transfected in the cell line (SHEP1) (Wu et al., 2004) PubMed:25514383
Subsequent to incubation with pM concentrations of Abeta1-42 monomers and oligomers, an increase of hippocampal LTP was observed PubMed:25514383
As with nicotine, the weak alpha7 nAChR agonist GTS-21 is neuroprotective, specifically protecting against Abeta1–42-elicited neurotoxicity154. This effect is probably due to small, protracted increases in receptor-mediated Ca2+ influx. importantly, high concentrations of GTS-21 reduced cell survival, underlining the possible risk of over-stimulation152 PubMed:19721446
Regardless of the exact effect of Abeta1–42 on receptor activity, it does seem to block the activation by nicotine and, consistent with the cytoprotective nature of this interaction, amyloid deposition limits neuroprotection151. This phenomenon may explain at least part of the neurotoxicity that is associated with Abeta1–42 (ReF. 156). PubMed:19721446
Regardless of the exact effect of Abeta1–42 on receptor activity, it does seem to block the activation by nicotine and, consistent with the cytoprotective nature of this interaction, amyloid deposition limits neuroprotection151. This phenomenon may explain at least part of the neurotoxicity that is associated with Abeta1–42 (ReF. 156). PubMed:19721446
Regardless of the exact effect of Abeta1–42 on receptor activity, it does seem to block the activation by nicotine and, consistent with the cytoprotective nature of this interaction, amyloid deposition limits neuroprotection151. This phenomenon may explain at least part of the neurotoxicity that is associated with Abeta1–42 (ReF. 156). PubMed:19721446
Concomitant cleavage of APP by beta and gamma secretase at specific sites can result in fragments (Abeta1-40 or Abeta1-42) that can misfold and form extracellular fibrils. PubMed:14556719
In a vicious circle, Aβ42 itself decreases IDE expression, although it may prompt its release from glia 254,259 . PubMed:30116051
Sixth, Aβ42 compro- mises the function of AMPK to impede initiation of the ALN 67 . PubMed:30116051
Sixth, Aβ42 compro- mises the function of AMPK to impede initiation of the ALN 67 . PubMed:30116051
Seventh, Aβ42 obstructs the UPS and CMA 47,68 . PubMed:30116051
Seventh, Aβ42 obstructs the UPS and CMA 47,68 . PubMed:30116051
The UPS and CMA are disrupted by neurotoxic proteins like Aβ42 and tau, hence, their early and preventive reinforcement prior to Aβ42 and tau accumulation may be critical. PubMed:30116051
The microtubule stabilizers paclitaxel and epothilone A countered Aβ42-induced cytoskeletal disruption — and moderated excessive UPR — in neurons 182 . PubMed:30116051
Neuronal expression of AK1 is upregulated in AD patients and is induced by Ab42 PubMed:22419736
Therefore, we examined whether oligomeric forms of Ab42 could regulate AK1 expression in neuronal cells. PubMed:22419736
From western blot analysis, we found that AK1 expression increased 2-fold in the cortical neurons after exposure to Ab42 PubMed:22419736
As shown in Figure 5A and B, treatment of control cells with Ab42 reduced the levels of AMPK phosphorylation at Thr172 and the inhibitory phosphorylation of GSK3b at Ser9. On the contrary, these alterations triggered by Ab42 were not observed in SH-SY5Y/AK1 knockdown cells, showing no changes in the levels of the phosphorylated AMPK and GSK3b. These results suggest that AK1 plays a crucial role in the regulation of AMPK and GSK3b in the neuronal cells exposed to Ab42. PubMed:22419736
A number of studies have found that Ab species, including oligomeric Ab42, are important factors responsible for tau pathogenesis PubMed:22419736
Interestingly, tau phosphor- ylation, which was detected by PHF-1 (Ser 396/404), CP13 (Ser 202) and 12E8 (Ser 262) antibodies, was also increased by Ab42 PubMed:22419736
Interestingly, tau phosphor- ylation, which was detected by PHF-1 (Ser 396/404), CP13 (Ser 202) and 12E8 (Ser 262) antibodies, was also increased by Ab42 PubMed:22419736
Interestingly, tau phosphor- ylation, which was detected by PHF-1 (Ser 396/404), CP13 (Ser 202) and 12E8 (Ser 262) antibodies, was also increased by Ab42 PubMed:22419736
Interestingly, tau phosphor- ylation, which was detected by PHF-1 (Ser 396/404), CP13 (Ser 202) and 12E8 (Ser 262) antibodies, was also increased by Ab42 PubMed:22419736
Among AK isoforms, AK2 was not detected in the primary neurons and HT22 cells, whereas AK3 expression was observed in the neurons but not regulated by Ab42 PubMed:22419736
When analyzed by reverse transcription-polymerase chain reaction, the level of AK1 mRNA, not AK1b mRNA, increased by Ab42 in primary neurons PubMed:22419736
Compared with control neurons, the effects of Ab42 on tau phosphorylation at CP13, PHF-1 and AT180 epitopes were significantly ameliorated in AK1 knockdown cortical neurons PubMed:22419736
Interestingly, treatment with Ab42 decreased the phosphorylation of AMPK at Thr172, whereas the total amount of AMPK was not altered in primary cortical neurons PubMed:22419736
Interestingly, treatment with Ab42 decreased the phosphorylation of AMPK at Thr172, whereas the total amount of AMPK was not altered in primary cortical neurons PubMed:22419736
We found, in addition, that enzyme activity of AMPK was sup- pressed in the cortical neurons after exposure to Ab42 PubMed:22419736
These results indicate that AMPK activity is impaired by Ab42 in the neuronal cells in which tau phosphor- ylation increased. PubMed:22419736
Consistently, the phosphorylation of acetyl Co-A carboxylase, a well-defined downstream substrate of AMPK, was also reduced by Ab42 PubMed:22419736
Given the size of AD-related proteins, mono- meric Aβ1-40, Aβ1-42 and tau, should be able to pass freely through astrocytic endfeet clefts at the glial barrier.72 PubMed:26195256
In addition, Aβ1–42 can increase the expression of TREM2, a surface signaling receptor in microglia, and the up-regulation of TRME2 can facilitate microglial phagocytosis of Aβ1–42 PubMed:29626319
By up-regulating endocytosis, high dietary LDL-cholesterol and overexpression of its receptor ApoE (particularly ApoE 14) elevate bCTF levels and increase delivery of Ab1–42 to lysosomes in cellular model systems (Ji et al. 2006; Cossec et al. 2010). PubMed:22908190
By up-regulating endocytosis, high dietary LDL-cholesterol and overexpression of its receptor ApoE (particularly ApoE 14) elevate bCTF levels and increase delivery of Ab1–42 to lysosomes in cellular model systems (Ji et al. 2006; Cossec et al. 2010). PubMed:22908190
By up-regulating endocytosis, high dietary LDL-cholesterol and overexpression of its receptor ApoE (particularly ApoE 14) elevate bCTF levels and increase delivery of Ab1–42 to lysosomes in cellular model systems (Ji et al. 2006; Cossec et al. 2010). PubMed:22908190
Consistent with these findings, strong overexpression of human Ab42, but not Ab40, in Drosophila neurons induces age-related accumulation of Ab in autolysosomes and neurotoxicity (Ling et al. 2009). PubMed:22908190
Consistent with these findings, strong overexpression of human Ab42, but not Ab40, in Drosophila neurons induces age-related accumulation of Ab in autolysosomes and neurotoxicity (Ling et al. 2009). PubMed:22908190
Ab42-induced neurotoxicity is further enhanced by autophagy activation and is partially rescued by autophagy inhibition. PubMed:22908190
Moreover, the level of A 1-42 was lowered by L-theanine and caused A 1-42- activated neuronal cell death in the cortex and hip-pocampus of the brain [128]. PubMed:29179999
Results have shown a sig- nificant increase in phosphorylation of IκB at serine 32–36 and NF-κB at serine 536 with Aβ 42 exposure, this phosphorylation enhances p65 transactivation potential [16]. PubMed:27288790
Results have shown a sig- nificant increase in phosphorylation of IκB at serine 32–36 and NF-κB at serine 536 with Aβ 42 exposure, this phosphorylation enhances p65 transactivation potential [16]. PubMed:27288790
Results have shown a sig- nificant increase in phosphorylation of IκB at serine 32–36 and NF-κB at serine 536 with Aβ 42 exposure, this phosphorylation enhances p65 transactivation potential [16]. PubMed:27288790
Aβ 42 mediated increase in BACE1 expression is accompanied by a decrease in Uch-L1 expression and activity in dif- ferent cellular models and in sporadic AD brains, which interferes with the lysosomal degradation of BACE1 [52,56]. PubMed:27288790
Upon exposure to various cell stressors including Aβ 42 , expression of BACE1-AS becomes elevated, increasing BACE1 mRNA stability and generating additional Aβ 42 through a post-transcriptional feed-forward mechanism [74]. PubMed:27288790
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
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
Exposure of primary neuronal cells or post-mitotic neurons to Aβ1-42 peptide has been shown to strongly activate the p50:p65 dimers and mediate neuronal cell death (Fig 1) PubMed:25652642
Exposure of primary neuronal cells or post-mitotic neurons to Aβ1-42 peptide has been shown to strongly activate the p50:p65 dimers and mediate neuronal cell death (Fig 1) 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
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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.