Embryonic Stem Cell-Derived Neurons as a Cellular System to Study Gene Function: Lack of Amyloid Precursor Proteins APP and APLP2 Leads to Defective Synaptic Transmission

Abstract

ABSTRACT

Amyloidosis and Neurodegenerative Diseases: Current Treatments and New Pharmacological Options

“…APP is a long-chain transmembrane protein, whose precise physiological function is not yet fully understood. Recent data strongly support a role for APP in embryonic neural organogenesis [19] , neurite outgrowth [20] and synaptogenesis [21] . Moreover, using proteomic and bioinformatic tools revealed that APP might interact with more than 30 proteins, suggesting that many physiological processes might be affected [22] .…”

Nuclear signaling by the APP intracellular domain occurs predominantly through the amyloidogenic processing pathway

“…It has been demonstrated that AICD possesses transactivation activity in luciferase assays (Cao and Sudhof, 2001), controls the expression of endogenous target genes (Alves da Costa et al, 2006;Baek et al, 2002;Belyaev et al, 2009;Liu et al, 2007;Muller et al, 2006;Pardossi-Piquard et al, 2005;Schrenk-Siemens et al, 2008;von Rotz et al, 2004;Zhang et al, 2007) and, together with Fe65 and Tip60, localizes to spherical nuclear complexes that are thought to represent sites of transcription (Konietzko et al, 2008;von Rotz et al, 2004). AICD can be generated from APP by two different proteolytic processing pathways and we have analyzed their differential nuclear signaling capacity.…”

Physiological Functions of APP Family Proteins

“…However, organotypic hippocampal slice cultures can be studied in case of early postnatal lethality. Of note, using this technique, APP/APLP2-DKO mutants revealed defects in basal glutamatergic synaptic transmission that were absent in single mutants (Schrenk-Siemens et al 2008). Thus, a more complete picture of APP/APLP function in the CNS will await the generation of brain specific conditional mutants.…”