scholarly journals Deposition of BACE-1 Protein in the Brains of APP/PS1 Double Transgenic Mice

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Gang Luo ◽  
Hongxia Xu ◽  
Yinuo Huang ◽  
Dapeng Mo ◽  
Ligang Song ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Protein Expression ◽  
Protein Accumulation ◽  
Significant Difference ◽  
Abnormal Accumulation ◽  
Double Transgenic Mice ◽  
Bace 1

The main causes of Alzheimer’s disease remain elusive. Previous data have implicated the BACE-1 protein as a central player in the pathogenesis of Alzheimer’s disease. However, many inhibitors of BACE-1 have failed during preclinical and clinical trials for AD treatment. Therefore, uncovering the exact role of BACE-1 in AD may have significant impact on the future development of therapeutic agents. Three- and six-month-old female APP/PS1 double transgenic mice were used to study abnormal accumulation of BACE-1 protein in brains of mice here. Immunofluorescence, immunohistochemistry, and western blot were performed to measure the distributing pattern and expression level of BACE-1. We found obvious BACE-1 protein accumulation in 3-month-old APP/PS1 mice, which had increased by the time of 6 months. Coimmunostaining results showed BACE-1 surrounded amyloid plaques in brain sections. The abnormal protein expression might not be attributable to the upregulation of BACE-1 protein, as no significant difference of protein expression was observed between wild-type and APP/PS1 mice. With antibodies against BACE-1 and CD31, we found a high immunoreactive density of BACE-1 protein on the outer layer of brain blood vessels. The aberrant distribution of BACE-1 in APP/PS1 mice suggests BACE-1 may be involved in the microvascular abnormality of AD.

scholarly journals STIM1 deficiency is linked to Alzheimer’s disease and triggers cell death in SH-SY5Y cells by upregulation of L-type voltage-operated Ca2+ entry

2018 ◽  
Vol 96 (10) ◽  
pp. 1061-1079 ◽  
Author(s):  
Carlos Pascual-Caro ◽  
Maria Berrocal ◽  
Aida M. Lopez-Guerrero ◽  
Alberto Alvarez-Barrientos ◽  
Eulalia Pozo-Guisado ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Death ◽  
Protein Expression ◽  
Transmembrane Domain ◽  
Neuroblastoma Cell ◽  
Disease Patient ◽  
List Type

Abstract STIM1 is an endoplasmic reticulum protein with a role in Ca2+ mobilization and signaling. As a sensor of intraluminal Ca2+ levels, STIM1 modulates plasma membrane Ca2+ channels to regulate Ca2+ entry. In neuroblastoma SH-SY5Y cells and in familial Alzheimer’s disease patient skin fibroblasts, STIM1 is cleaved at the transmembrane domain by the presenilin-1-associated γ-secretase, leading to dysregulation of Ca2+ homeostasis. In this report, we investigated expression levels of STIM1 in brain tissues (medium frontal gyrus) of pathologically confirmed Alzheimer’s disease patients, and observed that STIM1 protein expression level decreased with the progression of neurodegeneration. To study the role of STIM1 in neurodegeneration, a strategy was designed to knock-out the expression of STIM1 gene in the SH-SY5Y neuroblastoma cell line by CRISPR/Cas9-mediated genome editing, as an in vitro model to examine the phenotype of STIM1-deficient neuronal cells. It was proved that, while STIM1 is not required for the differentiation of SH-SY5Y cells, it is absolutely essential for cell survival in differentiating cells. Differentiated STIM1-KO cells showed a significant decrease of mitochondrial respiratory chain complex I activity, mitochondrial inner membrane depolarization, reduced mitochondrial free Ca2+ concentration, and higher levels of senescence as compared with wild-type cells. In parallel, STIM1-KO cells showed a potentiated Ca2+ entry in response to depolarization, which was sensitive to nifedipine, pointing to L-type voltage-operated Ca2+ channels as mediators of the upregulated Ca2+ entry. The stable knocking-down of CACNA1C transcripts restored mitochondrial function, increased mitochondrial Ca2+ levels, and dropped senescence to basal levels, demonstrating the essential role of the upregulation of voltage-operated Ca2+ entry through Cav1.2 channels in STIM1-deficient SH-SY5Y cell death. Key messages STIM1 protein expression decreases with the progression of neurodegeneration in Alzheimer’s disease. STIM1 is essential for cell viability in differentiated SH-SY5Y cells. STIM1 deficiency triggers voltage-regulated Ca2+ entry-dependent cell death. Mitochondrial dysfunction and senescence are features of STIM1-deficient differentiated cells.

Effect of Plant Compound Curcumin on the Expression of a-Synuclein in Hippocampal Neurons of APPswe/PS1dE9 Double Transgenic Mice

2013 ◽  
Vol 781-784 ◽  
pp. 643-646
Author(s):  
Xiao Lin ◽  
Li Yu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Hippocampal Neurons ◽  
Neuroprotective Effect ◽  
Disease Model ◽  
Dependent Manner ◽  
Double Transgenic Mice ◽  
Ad Alzheimer’S Disease ◽  
Dose Dependent

In this study, we aim to investigate the effect of curcumin on the expression of a-synuclein in the APPswe/PS1dE9 double transgenic mice. APPswe/PS1dE9 double transgenic mice were used as AD (Alzheimer's disease) model and fed with different concentrations of curcumin every day for 6 months, then immunohistochemistry method were used to detect the expression of a-synuclein in hippocampus of mice. The expression of a-syn in hippocampal neuron was decreased significantly after treated with 0.16g/kg to 1.0g/kg curcumin, the change was apparent in dose-dependent manner (P<0.05). a-synuclein pay an important role in the genesis and development of Alzheimer's disease and decreased level of a-synuclein might contribute to the neuroprotective effect of Curcumin, which may become a new target for the prevention and treatment of Alzheimer's disease.

scholarly journals Delta-secretase triggers Alzheimer’s disease pathologies in wild-type hAPP/hMAPT double transgenic mice

2020 ◽  
Vol 11 (12) ◽  
Author(s):  
Zhourui Wu ◽  
Xia Liu ◽  
Liming Cheng ◽  
Keqiang Ye
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Senile Plaques ◽  
Wild Type ◽  
Double Transgenic Mouse ◽  
Double Transgenic Mice ◽  
One Year ◽  
Aβ Production ◽  
Human Wild Type

AbstractAlzheimer’s disease (AD) is the most common neurodegenerative disease with multifactorial pathologies including Aβ containing senile plaques and neurofibrillary tangles (NFT) consisted of aggregated Tau. Most of the AD patients are sporadic and the familial mutation hereditary patients are composed only 1% of all cases. However, the current AD mouse models employ mutated APP, PS1, or even Tau mutant, in order to display a portion of AD pathologies. Delta-secretase (legumain, or asparaginyl endopeptidase, AEP) simultaneously cleaves both APP and Tau and augments Aβ production and Tau hyperphosphorylation and aggregation, contributing to AD pathogenesis. Here we show that δ-secretase is sufficient to promote prominent AD pathologies in wild-type hAPP/hMAPT double transgenic mice. We crossed hAPP l5 mice and hMAPT mice to generate double transgenic mouse model carrying both human wild-type APP and Tau. Compared to the single transgenic parents, these double transgenic mice demonstrated AD-related pathologies in one-year-old hAPP/hMAPT mice. Notably, overexpression of δ-secretase in hAPP/hMAPT double-transgenic mice evidently accelerated enormous senile plaques and NFT, associated with prominent synaptic defects and cognitive deficits. Hence, δ-secretase facilitates AD pathogenesis independent of any patient-derived mutation.

scholarly journals Banxia Xiexin decoction ameliorated cognition via the regulation of insulin pathways and glucose transporters in the hippocampus of APPswe/PS1dE9 mice

2018 ◽  
Vol 32 ◽  
pp. 205873841878006 ◽  
Author(s):  
Fang Chen ◽  
Yingkun He ◽  
Pengwen Wang ◽  
Peng Wei ◽  
Huili Feng ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Synaptic Plasticity ◽  
Glucose Metabolism ◽  
Transgenic Mice ◽  
Cognitive Performance ◽  
Insulin Signalling ◽  
Glucose Transporter 1 ◽  
Double Transgenic Mice ◽  
Banxia Xiexin Decoction

Reduced glucose utilization and deficient energy metabolism that occur in the early stages of Alzheimer’s disease correlate with impaired cognition, and this information is evidence that Alzheimer’s disease is a metabolic disease that is associated with brain insulin/insulin-like growth factor resistance. This research aimed to investigate the effects of Banxia Xiexin decoction (BXD) on cognitive deficits in APPswe/PS1dE9 double transgenic mice and verify the hypothesis that BXD treatment improves cognitive function via improving insulin signalling, glucose metabolism and synaptic plasticity in the hippocampus of APPswe/PS1dE9 double transgenic mice. We used 3-month-old APPswe/PS1dE9 double transgenic mice as the case groups and wild-type littermates of the double transgenic mice from the same colony as the control group. Forty-five APPswe/PS1dE9 double transgenic mice were randomly divided into the model group, donepezil group and BXD group. The mice in the control and model groups were administered 0.5% carboxymethyl cellulose orally. The Morris water maze and step-down test were conducted to evaluate the cognitive performance of APPswe/PS1dE9 double transgenic mice after BXD treatment. Ultrastructure of synapses was observed in the hippocampal CA1 area. Proteins involved in insulin signalling pathways and glucose transports in the hippocampus were assessed through immunohistochemical staining and western blot. After 3 months intervention, we found that BXD treatment improved cognitive performance and the synaptic quantity and ultrastructure, restored insulin signalling and increased the expression of glucose transporter 1 (GLUT1) and GLUT3 levels. These findings suggest that the beneficial effect of BXD on cognition may be due to the improvement of insulin signalling, glucose metabolism and synaptic plasticity.

Exercise and probiotics attenuate the development of Alzheimer's disease in transgenic mice: Role of microbiome

2019 ◽  
Vol 115 ◽  
pp. 122-131 ◽  
Author(s):  
Dora Abraham ◽  
Janos Feher ◽  
Gian Luca Scuderi ◽  
Dora Szabo ◽  
Arpad Dobolyi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice

P3-149: Protein expression in the brain of transgenic mice models of Alzheimer's disease

2011 ◽  
Vol 7 ◽  
pp. S564-S564
Author(s):  
Manuela Fritsch ◽  
Daniela Volke ◽  
Ralf Hoffmann ◽  
David Singer
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Protein Expression ◽  
The Brain

The role of alpha-1-antichymotrypsin (ACT) in abeta-amyloidosis of Alzheimer's disease, as studied in novel trigenic PDAPP, mapoe-knockout, GFAP-hACT transgenic mice strains

2000 ◽  
Vol 21 ◽  
pp. 88
Author(s):  
Lars Ng Nilsson ◽  
Giovanni DiCarlo ◽  
Marcia N. Gordon ◽  
David G. Morgan ◽  
Kelly R. Bales ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice
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