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ApoE4 genotype is the most prevalent and also clinically most important risk factor for late-onset Alzheimer's disease (AD). Available evidence suggests that the root cause for this increased risk is a trafficking defect at the level of the early endosome. ApoE4 differs from the most common ApoE3 isoform by a single amino acid that increases its isoelectric point and promotes unfolding of ApoE4 upon endosomal vesicle acidification. We found that pharmacological and genetic inhibition of NHE6, the primary proton leak channel in the early endosome, in rodents completely reverses the ApoE4-induced recycling block of the ApoE receptor Apoer2/Lrp8 and the AMPA- and NMDA-type glutamate receptors that are regulated by, and co-endocytosed in a complex with, Apoer2. Moreover, NHE6 inhibition restores the Reelin-mediated modulation of excitatory synapses that is impaired by ApoE4. Our findings suggest a novel potential approach for the prevention of late-onset AD.
Pubmed ID: 30375977 RIS Download
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Mus musculus with name C57BL/6J from IMSR.
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View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)
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View all literature mentionsThis polyclonal targets Apolipoprotein E
View all literature mentionsCell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis polyclonal targets GRIA1
View all literature mentionsThis polyclonal targets NMDAR2B
View all literature mentionsThis polyclonal targets Transferrin Receptor antibody
View all literature mentionsThis polyclonal targets GluR2 / GluR3
View all literature mentionsThis monoclonal targets Phosphotyrosine
View all literature mentionsVector graphics software to create digital graphics, illustrations, and typography for several types of media: print, web, interactive, video, and mobile.
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsHigh resolution, compact and robust confocal that enables immunohistochemical colocalization analysis of florescent markers.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsA development environment for engineers and scientists to visualize, create, and code engineering systems. The system design software is integrated with all measurement hardware and contains signal processing IP. Other features include multithreaded execution, software deployment to hardware, and program integration into a single environment.
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View all literature mentionsSoftware package as distribution of ImageJ and ImageJ2 together with Java, Java3D and plugins organized into coherent menu structure. Used to assist research in life sciences.
View all literature mentionsA data analysis software developed to simplify and record data from fluorescent related assays such as Western Blots, EMSAs, and Western Assays. This software will consolidate all of the resulting data into one easy-to-track image, and thus removes the need for multiple exposures, as well as standardizing the resulting fluorescent bands without image saturation, blowout, or removed sensitivity. Odyssey CLx is capable of scanning multiple mini-blots, microplates, or slides at the same time.
View all literature mentionsThis polyclonal targets RCJMB04_4h19
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