The present study evaluates the impact of neurosteroids belonging to the sex hormone family (progesterone, estradiol, estrone, testosterone, 3α-androstanediol) on mitochondrial dysfunction in cellular models of AD: human neuroblastoma cells (SH-SY5Y) stably transfected with constructs encoding (1) the human amyloid precursor protein (APP) resulting in overexpression of APP and Aβ, (2) wild-type tau (wtTau), and (3) mutant tau (P301L), that induces abnormal tau hyperphosphorylation.
Here, we found that S-nitrosylation of O-linked N-acetylglucosaminyltransferase (SNO-OGT) was induced by β-amyloid peptide (Aβ) exposure to SK-N-MC and SK-N-SH human neuroblastoma cells.
To determine the role of ANXA1 in the processing of amyloid precursor protein (APP) and the degradation of Aβ, N2a neuroblastoma cells were treated with human recombinant ANXA1 or transfected with ANXA1 siRNA.
SH-SY5Y neuroblastoma cells transfected with the amyloid precursor protein (APP) gene containing the Swedish mutations causing familial AD (APPswe), were used as a model to explore the effect of Aβ pathology on 5-HT1B and related molecules including the receptor adaptor protein (p11), SERT and MAOA gene expression, and MAOA activity after treatment with selective serotonin reuptake inhibitor (SSRI) (sertraline), and a 5-HT1B receptor antagonist.
We investigated the effect of the familial AD APP (Amyloid precursor protein) K670N/M671L double mutation, APP Swedish mutation (APPswe), on the expression of 5-HT1B, SERT, MAOA, p11 and 5-HT and its metabolite 5-HIAA in SH-SY5Y human neuroblastoma cell line stably transfected with APPswe mutation.
The aim of the present study is to examine the ability of GW7647 (a PPAR-α agonist) to regulate amyloid precursor protein (APP) amyloidogenic processing in human neuroblastoma SH-SY5Y cells transfected with APPswe gene.
Using differentiated neuroblastoma SH-SY5Y cells, we showed that Omi/HtrA2 under several different stress conditions induces cleavage of vimentin in wild-type as well as SH-SY5Y cells transfected with amyloid precursor protein with the Alzheimer disease-associated Swedish mutation.
Here we show that treatment with HLJDT-M and its components RC, CP, and the main compound berberine on N2a mouse neuroblastoma cells stably expressing human APP with the Swedish mutation (N2a-SwedAPP) significantly decreased the levels of full-length APP, phosphorylated APP at threonine 668, C-terminal fragments of APP, soluble APP (sAPP)-α and sAPPβ-Swedish and reduced the generation of Aβ peptide in the cell lysates of N2a-SwedAPP.
Recombinant lentiviral vectors were used to overexpress GDNF gene in hippocampal astrocytes of 3xTg-AD mice in vivo, and also in the MC65 human neuroblastoma that conditionally overexpresses the 99-residue carboxyl-terminal (C99) fragment of the amyloid precursor protein.
Gamma-hydroxybutyrate, acting through an anti-apoptotic mechanism, protects native and amyloid-precursor-protein-transfected neuroblastoma cells against oxidative stress-induced death.
By utilizing neuroblastoma N2a cells transfected with Swedish mutated human amyloid precursor protein (APP) (N2a/APPswe) and wild-type APP (N2a/APPwt) as cellular models of AD, we examined the alterations of histone acetylation at the promoter regions of PS1 and BACE1 in these cells.
Using human neuroblastoma (SHSY5Y) cells, we first silenced RNA for APP, Tau, and VDAC1 genes, and then performed real-time RT-PCR analysis to measure mRNA levels of 34 genes that are involved in AD pathogenesis.
Although BIN1 is known to have a role in endocytosis, and the processing of the amyloid precursor protein (APP) to form amyloid-β (Aβ) peptides is dependent on endocytosis, knockdown of BIN1 by targeted siRNA or the overexpression of BIN1 in a human neuroblastoma cell line (SH-SY5Y) had no effect on APP processing.
In this study, we further characterize the interactions between Hb and Aβ in vitro and in vivo and report the following observations: 1) the binding of Hb to Aβ required iron-containing heme; 2) other heme-containing proteins, such as myoglobin and cytochrome C, also bound to Aβ; 3) hemin-induced cytotoxicity was reduced in neuroblastoma cells by low levels of Aβ; 4) Hb was detected in neurons and glial cells of post-mortem AD brains and was up-regulated in aging and APP/PS1 transgenic mice; 5) microinjection of human Hb into the dorsal hippocampi of the APP/PS1 transgenic mice induced the formation of an envelope-like structure composed of Aβ surrounding the Hb droplets.
We show that overexpression of wild-type human APP (APP(695)), or APP harboring the Swedish double mutation (APP(swe)) triggers increased ryanodine receptor (RyR) expression and enhances RyR-mediated ER Ca²⁺ release in SH-SY5Y neuroblastoma cells and in APP(swe)-expressing (Tg2576) mice.
Increased expression of LRP10 in human neuroblastoma SH-SY5Y cells induces the accumulation of mature APP in the Golgi and reduces its presence at the cell surface and its processing into Aβ, while knockdown of LRP10 expression increases Aβ production.
Results from this investigation suggest that the ADAM10 rs514049-rs653765 C-A promoter haplotype is associated with: (1) higher CSF sAPPα levels in cognitively normal controls compared with Alzheimer's disease (AD) patients, (2) higher postmortem brain hippocampus, but not cerebellum, ADAM10 protein levels in subjects with low plaque scores compared with those with high plaque scores, and (3) higher promoter activity for promoter-only reporter constructs compared with promoter 3' untranslated region (3'UTR) constructs in the human neuroblastoma SHSY5Y cell line, but not in HepG2 or U118 cell lines.
Here, we show that the neurotransmitter dopamine stimulates the rapid endocytosis and processing of APP and induces apoptosis in neuroblastoma Neuro2A cells over-expressing transgenic human APP (Swedish mutant).