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Search results for: APP (Phospho-Thr668) Antibody

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#33625628   2021/02/24 To Up

Main Role of Antibodies in Demyelination and Axonal Damage in Multiple Sclerosis.

Antibodies and oxidative stress are hallmarks of multiple sclerosis (MS) lesions. We aimed to clarify the relation between them, their role in MS patients and to investigate their specificity, comparing MS with classical neurodegenerative diseases (ND). Brain samples from 14 MS cases, 6 with ND and 9 controls (without neurological diseases). Immunohistochemistry assays were used to detect oxidized lipids (EO6), IgG and IgM, oligodendrocytes (Olig2), axons (NF, neurofilament) and cellular (TUNEL) and axonal damage (APP, amyloid precursor protein). We did not observe EO6 in controls. All samples from MS patients showed EO6 in oligodendrocytes and axons within lesions. We did not detect co-localization between EO6 and antibodies. Neither did we between EO6 and TUNEL or APP. 94.4% of TUNEL-positive cells in normal appearing white matter were also stained for IgG and 75.5% for IgM. IgM, but not IgG, co-localized with APP. EO6 was associated with axonal damage in amyotrophic lateral sclerosis (ALS). We did not observe association between antibodies and cellular or axonal damage in ND patients. MS patients showed a higher number of B cells and plasma cells in the lesions and meninges than controls. The number of B cells and plasma cells was associated with the presence of antibodies and with the activity of the lesions. We observed a main role of B lymphocytes in the development of MS lesions. Antibodies contribute to the oligodendrocyte and axonal damage in MS. Oxidative stress was associated with axonal damage in ALS.
Ursula Muñoz, Cristina Sebal, Esther Escudero, Margaret Esiri, John Tzartos, Carolyn Sloan, Mari Cruz Sadaba

2489 related Products with: Main Role of Antibodies in Demyelination and Axonal Damage in Multiple Sclerosis.

100 μg100 μg4 Arrays/Slide100 μg100 μg100.00 ug100 μg1 ml100 μg100 μg

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#33608391   2021/02/15 To Up

Flexible and accurate substrate processing with distinct presenilin/γ-secretases in human cortical neurons.

Mutations in the genes (, ) have been linked to the majority of familial Alzheimer's disease (AD). Although great efforts have been made to investigate pathogenic mutations, which ultimately cause an increase in the toxic form of β-amyloid (Aβ), the intrinsic physiological functions of PS in human neurons remain to be determined. In this study, to investigate the physiological roles of PS in human neurons, we generated conditional knockout induced pluripotent stem cells (iPSCs), in which PS1 can be selectively abrogated under Cre transduction with or without additional knockout. We showed that iPSC-derived neural progenitor cells do not confer a maintenance ability in the absence of both PS1 and PS2, showing the essential role of PS in Notch signaling. We then generated -null human cortical neurons, where PS1 was intact until full neuronal differentiation occurred. Aβ40 production was reduced exclusively in human /-null neurons along with a concomitant accumulation of APP-CTFs, whereas Aβ42 was decreased in neurons devoid of Unlike previous studies in mice, in which APP cleavage is largely attributable to PS1, γ-secretase activity seemed to be comparable between PS1 and PS2. In contrast, cleavage of another substrate, N-cadherin, was impaired only in neurons devoid of Moreover, PS2/γ-secretase exists largely in late endosomes/lysosomes, as measured by specific antibody against the γ-secretase complex, in which Aβ42 species are supposedly produced. Using this novel stem cell-based platform, we assessed important physiological PS1/PS2 functions in mature human neurons, the dysfunction of which could underlie AD pathogenesis. Presenilins are crucial catalytic subunits of γ-secretase, an intramembranous protease complex, whose mutations underlie AD pathogenesis via the dysregulation of Aβ generation. The γ-secretase complex exhibits heterogeneity via the assembly of PS1 or PS2, but the correlation of γ-secretase heterogeneity with substrate processing remains to be established in human neurons. Here, using a novel iPSC-derived cellular model carrying and/or conditional knockout alleles, we uncovered the unique processing of three substrates, Notch, APP and N-cadherin, by PS1 or PS2 in human neural cell contexts. Furthermore, the intrinsic subcellular localization of γ-secretase depends on PS1 or PS2, leading to putative differences in the processing of substrates. This novel platform will help ensure the correlation of γ-secretase/substrates in human neurons.
Hirotaka Watanabe, Kent Imaizumi, Tetsuo Cai, Zhi Zhou, Taisuke Tomita, Hideyuki Okano

1245 related Products with: Flexible and accurate substrate processing with distinct presenilin/γ-secretases in human cortical neurons.

100 μg100 μg100 μg100.00 ug10 100 μgOne 96-Well Strip Micropl100 μg10ug4 Arrays/Slide100 μg5 mg

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#33584493   2021/01/13 To Up

Operation Brain Trauma Therapy: An Exploratory Study of Levetiracetam Treatment Following Mild Traumatic Brain Injury in the Micro Pig.

Operation brain trauma therapy (OBTT) is a drug- and biomarker-screening consortium intended to improve the quality of preclinical studies and provide a rigorous framework to increase the translational potential of experimental traumatic brain injury (TBI) treatments. Levetiracetam (LEV) is an antiepileptic agent that was the fifth drug tested by OBTT in three independent rodent models of moderate to severe TBI. To date, LEV has been the most promising drug tested by OBTT and was therefore advanced to testing in the pig. Adult male micro pigs were subjected to a mild central fluid percussion brain injury followed by a post-injury intravenous infusion of either 170 mg/kg LEV or vehicle. Systemic physiology was assessed throughout the post-injury period. Serial serum samples were obtained pre-injury as well as at 1 min, 30 min, 1 h, 3 h, and 6 h post-injury for a detailed analysis of the astroglial biomarker glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1. Tissue was collected 6 h following injury for histological assessment of diffuse axonal injury using antibodies against the amyloid precursor protein (APP). The animals showed significant increases in circulating GFAP levels from baseline to 6 h post-injury; however, LEV treatment was associated with greater GFAP increases compared to the vehicle. There were no differences in the numbers of APP+ axonal swellings within the pig thalamus with LEV treatment; however, significant alterations in the morphological properties of the APP+ axonal swellings, including reduced swelling area and increased swelling roundness, were observed. Additionally, expression of the neurite outgrowth marker, growth-associated protein 43, was reduced in axonal swellings following LEV treatment, suggesting potential effects on axonal outgrowth that warrant further investigation.
Audrey Lafrenaye, Stefania Mondello, John Povlishock, Karen Gorse, Susan Walker, Ronald Hayes, Kevin Wang, Patrick M Kochanek

2231 related Products with: Operation Brain Trauma Therapy: An Exploratory Study of Levetiracetam Treatment Following Mild Traumatic Brain Injury in the Micro Pig.

50ug50ug 50 UG1.00 kit100 μg

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#33575481   2020/12/17 To Up

Can Anti-β-amyloid Monoclonal Antibodies Work in Autosomal Dominant Alzheimer Disease?

The dominant theory of Alzheimer disease (AD) has been that amyloid-β (Aβ) accumulation in the brain is the initial cause of the degeneration leading to cognitive and functional deficits. Autosomal dominant Alzheimer disease (ADAD), in which pathologic mutations of the amyloid precursor protein () or presenilins () genes are known to cause abnormalities of Aβ metabolism, should thus offer perhaps the best opportunity to test anti-Aβ drugs. Two long-term preventive studies (Dominantly Inherited Alzheimer Network Trials Unit Adaptive Prevention Trial [DIAN-TU-APT] and Alzheimer Preventive Initiative-ADAD) were set up to evaluate the efficacy of monoclonal anti-Aβ antibodies (solanezumab, gantenerumab, and crenezumab) in carriers of ADAD, but the results of the DIAN-TU-APT study have shown that neither solanezumab nor gantenerumab slowed cognitive decline in 144 subjects with ADAD followed for 4 years, despite one of the drugs (gantenerumab) significantly affected biomarkers relevant to their intended mechanism of action. Surprisingly, solanezumab significantly accelerated cognitive decline of both asymptomatic and symptomatic subjects. These failures further undermine the Aβ hypothesis and could support the suggestion that ADAD is triggered by accumulation of other APP metabolites, rather than Aβ.
Bruno P Imbimbo, Ugo Lucca, Mark Watling

1623 related Products with: Can Anti-β-amyloid Monoclonal Antibodies Work in Autosomal Dominant Alzheimer Disease?

100 ul100.00 ug100 ul100.00 ug96 tests100.00 ug100.00 ug100 μg50 ul100.00 ug100.00 ug100.00 ug

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#33519090   2020/12/14 To Up

Paper biosensors for detecting elevated IL-6 levels in blood and respiratory samples from COVID-19 patients.

Decentralizing COVID-19 care reduces contagions and affords a better use of hospital resources. We introduce biosensors aimed at detecting severe cases of COVID-19 in decentralized healthcare settings. They consist of a paper immunosensor interfaced with a smartphone. The immunosensors have been designed to generate intense colorimetric signals when the sample contains ultralow concentrations of IL-6, which has been proposed as a prognosis biomarker of COVID-19. This is achieved by combining a paper-based signal amplification mechanism with polymer-filled reservoirs for dispensing antibody-decorated nanoparticles and a bespoken app for color quantification. With this design we achieved a low limit of detection (LOD) of 10 pg mL and semi-quantitative measurements in a wide dynamic range between 10 and 10 pg mL in PBS. The assay time is under 10 min. The low LOD allowed us to dilute blood samples and detect IL-6 with an LOD of 1.3 pg mL and a dynamic range up to 10 pg mL. Following this protocol, we were able to stratify COVID-19 patients according to different blood levels of IL-6. We also report on the detection of IL-6 in respiratory samples (bronchial aspirate, BAS) from COVID-19 patients. The test could be easily adapted to detect other cytokines such as TNF-α and IL-8 by changing the antibodies decorating the nanoparticles accordingly. The ability of detecting cytokines in blood and respiratory samples paves the way for monitoring local inflammation in the lungs as well as systemic inflammation levels in the body.
Cristina Adrover-Jaume, Alejandra Alba-Patiño, Antonio Clemente, Giulia Santopolo, Andreu Vaquer, Steven M Russell, Enrique Barón, María Del Mar González Del Campo, Joana M Ferrer, María Berman-Riu, Mercedes García-Gasalla, María Aranda, Marcio Borges, Roberto de la Rica

2507 related Products with: Paper biosensors for detecting elevated IL-6 levels in blood and respiratory samples from COVID-19 patients.

96 tests10 mg96 samples 100 G100ug Lyophilized100 extractions100 mg

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#33499548   // To Up

Paper-Based Microfluidic Devices: Low-Cost Platforms for Rapid Biochemical Detection.

We developed low-cost, portable paper-based diagnostic devices for detection of human immunoglobulin M (IgM) and immunoglobulin G (IgG) in serum without any sample preparation. These devices can be used to help identify presence of diseases, used to provide rapid results (<5 minutes), readily used by untrained personnel, employed in austere environments, configured to obtain multiplexed assays, and easily disposed of.
Bariş Ünal, Gulden Camci-Unal, Ken Mahmud

2567 related Products with: Paper-Based Microfluidic Devices: Low-Cost Platforms for Rapid Biochemical Detection.

2x96 well plate500 One 96-Well Microplate Ki100ug 96 Tests 100μg2x96 well plate96 Well10 mg96 tests 500 ml

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#33413577   2021/01/07 To Up

Cell surface GRP78 regulates BACE2 via lysosome-dependent manner to maintain mesenchymal phenotype of glioma stem cells.

Glioma stem cells (GSCs) are considered the initial cells of gliomas, contributing to therapeutic resistance. Patient-derived GSCs well recapitulate the heterogeneity of their parent glioma tissues, which can be classified into different subtypes. Likewise, previous works identified GSCs as two distinct subtypes, mesenchymal (MES) and proneural (PN) subtypes, and with general recognition, the MES subtype is considered a more malignant phenotype characterized by high invasion and radioresistance. Therefore, understanding the mechanisms involved in the MES phenotype is necessary for glioblastoma treatment.
Zihang Chen, Huizhi Wang, Zongpu Zhang, Jianye Xu, Yanhua Qi, Hao Xue, Zijie Gao, Rongrong Zhao, Shaobo Wang, Shouji Zhang, Wei Qiu, Xing Guo, Gang Li

2240 related Products with: Cell surface GRP78 regulates BACE2 via lysosome-dependent manner to maintain mesenchymal phenotype of glioma stem cells.

5 x 10A5 cells/vial1 vial1 x 10^6 cells/vial10 ug100ìl x 10 vials24 wells24 wells1.00 flask24 wells100 extractions100 ug/vial

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#33403386   2021/01/05 To Up

Reversal of apolipoprotein E4-dependent or chemical-induced accumulation of APP degradation products by vitamin C-induced release of heparan sulfate from glypican-1.

The Apolipoprotein E4 (ApoE4) genotype is the most influential risk factor for sporadic Alzheimer's disease. It appears to be associated with retarded endosome-to-autophagosome trafficking. The amyloid precursor protein (APP) and the heparan sulfate (HS)-containing proteoglycan glypican-1 (Gpc-1) are both processed in endosomes, and mutually regulated by the APP degradation products and the released HS. We have investigated APP and Gpc-1 processing in ApoE3 and ApoE4 expressing human fibroblasts, in human neural stem cells (NSC) exposed to the cholesterol transport inhibitor U18666A and in induced neurons obtained by reprogramming of ApoE fibroblasts (ApoE-iN). We have used immunofluorescence microscopy, flow cytometry, and SDS-PAGE-western blotting with antibodies recognizing the released HS, APP, amyloid ᵝ(Aᵝ), late endosomes (Rab7), autophagosomes (LC3) and neurons (Tuj1). We found that the capacity to release HS was not fully utilized in ApoE4 expressing fibroblasts and that HS-Aᵝ complexes accumulated in the nuclei. In ApoE3 fibroblasts, the ᵝ-cleaved APP C-terminal fragment (ᵝ-CTF) and Aᵝ were primarily present in late endosomes and autophagosomes. When HS release from Gpc-1 was enhanced by ascorbate in ApoE4/4 fibroblasts, there was efficient transfer of Aᵝ and HS from the nuclei to autophagosomes. In U18666A-treated NSC as well as in ApoE4/4-iN we repeatedly found accumulation of APP degradation products (ᵝ-CTF/Aᵝ). This was reversed by subsequent exposure to ascorbate or dehydroascorbic acid.
Fang Cheng, Lars-Åke Fransson, Katrin Mani

1743 related Products with: Reversal of apolipoprotein E4-dependent or chemical-induced accumulation of APP degradation products by vitamin C-induced release of heparan sulfate from glypican-1.

5 G 100ul400 ug100 mg25 mg0.1 mg100ug Lyophilized50ul (1mg/ml)25 mg1 g96T50ul (1mg/ml)

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