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10.1186/s13041-015-0129-7 http://scihub22266oqcxt.onion/10.1186/s13041-015-0129-7 C4501290!4501290!26170135     free     free     free Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Mol+Brain 2015 ; 8 (ä): ä Nephropedia Template TP {{tp|p=26170135|t=2015. Arf6 controls beta-amyloid production by regulating macropinocytosis of the Amyloid Precursor Protein to lysosomes |pdf=|usr=}}{{26170135}} gab.com Text Arf6 controls beta-amyloid production by regulating macropinocytosis of the Amyloid Precursor Protein to lysosomes JO: Mol Brain http://www.kidney.de/pget.php?&tw=1&pmid=26170135 #FOAvip Alzheimer?s disease (AD) is characterized by the deposition of Beta-Amyloid (A?) peptides in the brain. A? peptides are generated by cleavage of the Amyloid Precursor Protein (APP) by the ????and ????secretase enzymes. Although this process is tightly linked to the internalization of cell surface APP, the compartments responsible are not well defined. We have found that APP can be rapidly internalized from the cell surface to lysosomes, bypassing early and late endosomes. Here we show by confocal microscopy and electron microscopy that this pathway is mediated by macropinocytosis. APP internalization is enhanced by antibody binding/crosslinking of APP suggesting that APP may function as a receptor. Furthermore, a dominant negative mutant of Arf6 blocks direct transport of APP to lysosomes, but does not affect classical endocytosis to endosomes. Arf6 expression increases through the hippocampus with the development of Alzheimer?s disease, being expressed mostly in the CA1 and CA2 regions in normal individuals but spreading through the CA3 and CA4 regions in individuals with pathologically diagnosed AD. Disruption of lysosomal transport of APP reduces both A?40 and A?42 production by more than 30 %. Our findings suggest that the lysosome is an important site for A? production and that altering APP trafficking represents a viable strategy to reduce A? production.Electronic supplementary material: The online version of this article (doi:10.1186/s13041-015-0129-7) contains supplementary material, which is available to authorized users. Twit Text FOAVip Arf6 controls beta-amyloid production by regulating macropinocytosis of the Amyloid Precursor Protein to lysosomes ????Mol Brain http://www.kidney.de/pget.php?&tw=1&pmid=26170135 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=26170135 #FOAvip English Wikipedia <ref>{{Cite pmid|26170135}}</ref> Arf6 controls beta-amyloid production by regulating macropinocytosis of the Amyloid Precursor Protein to lysosomes #MMPMID26170135 Tang W; Tam JH; Seah C; Chiu J; Tyrer A; Cregan SP; Meakin SO; Pasternak SH Mol Brain 2015[]; 8 (ä): ä PMID26170135show ga Alzheimer?s disease (AD) is characterized by the deposition of Beta-Amyloid (A?) peptides in the brain. A? peptides are generated by cleavage of the Amyloid Precursor Protein (APP) by the ????and ????secretase enzymes. Although this process is tightly linked to the internalization of cell surface APP, the compartments responsible are not well defined. We have found that APP can be rapidly internalized from the cell surface to lysosomes, bypassing early and late endosomes. Here we show by confocal microscopy and electron microscopy that this pathway is mediated by macropinocytosis. APP internalization is enhanced by antibody binding/crosslinking of APP suggesting that APP may function as a receptor. Furthermore, a dominant negative mutant of Arf6 blocks direct transport of APP to lysosomes, but does not affect classical endocytosis to endosomes. Arf6 expression increases through the hippocampus with the development of Alzheimer?s disease, being expressed mostly in the CA1 and CA2 regions in normal individuals but spreading through the CA3 and CA4 regions in individuals with pathologically diagnosed AD. Disruption of lysosomal transport of APP reduces both A?40 and A?42 production by more than 30 %. Our findings suggest that the lysosome is an important site for A? production and that altering APP trafficking represents a viable strategy to reduce A? production.Electronic supplementary material: The online version of this article (doi:10.1186/s13041-015-0129-7) contains supplementary material, which is available to authorized users. äArf6 controls beta-amyloid production by regulating macropinocytosis o(epmc).pdf DeepDyve Pubget Overpricing