DOI: 10.1101/504340Dec 21, 2018Paper

Amyloid Precursor Protein (APP) controls excitatory/inhibitory synaptic inputs by regulating the transcriptional activator Neuronal PAS Domain Protein 4 (NPAS4)

BioRxiv : the Preprint Server for Biology
Remi OpsomerPascal Kienlen-Campard

Abstract

Sequential proteolysis of the amyloid precursor protein (APP) and amyloid-beta petide (Abeta) release is an upstream event in Alzheimer's disease (AD) pathogenesis. The function of APP in neuronal physiology is still, however, poorly understood. Along with its paralog APP-like Proteins 1 and 2 (APLP1-2), APP is involved in neurite formation and synaptic function by mechanisms that are not elucidated. APP is a single-pass transmembrane protein expressed at high levels in the brain that resembles a cell adhesion molecule or a membrane receptor, suggesting that its function relies on cell interaction processes and/or activation of intracellular pathways of signal transduction. Along this line, the APP intracellular domain (AICD) was reported to act as a transcriptional factor for targeted gene activation that mediates physiological APP functions. Here, we used an unbiased transcriptome-based approach to identify the genes transcriptionally regulated by APP in the rodent embryonic cortex and upon maturation of primary cortical neurons. The transcriptome analysis did not detect any significant differences in expression of previously proposed AICD target genes. The overall transcriptional changes were subtle, but we found that genes ...Continue Reading

Related Concepts

Alzheimer's Disease
Brain
Cell Adhesion
Cell Communication
Down-Regulation
Embryo
Gene Activation
Genes
Integral Membrane Proteins
Synaptic Transmission

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