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Molecular Neurodegeneration
Published in: Molecular Neurodegeneration 1/2016

Open Access 01-12-2016 | Research article

The novel RAGE interactor PRAK is associated with autophagy signaling in Alzheimer’s disease pathogenesis

Authors: Yoonhee Kim, Chaeyoung Kim, Sung Min Son, Hyundong Song, Hyun Seok Hong, Sun-ho Han, Inhee Mook-Jung

Published in: Molecular Neurodegeneration | Issue 1/2016

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Abstract

Background

The receptor for advanced glycation end products (RAGE) has been found to interact with amyloid β (Aβ). Although RAGE does not have any kinase motifs in its cytosolic domain, the interaction between RAGE and Aβ triggers multiple cellular signaling involved in Alzheimer’s disease (AD). However, the mechanism of signal transduction by RAGE remains still unknown. Therefore, identifying binding proteins of RAGE may provide novel therapeutic targets for AD.

Results

In this study, we identified p38-regulated/activated protein kinase (PRAK) as a novel RAGE interacting molecule. To investigate the effect of Aβ on PRAK mediated RAGE signaling pathway, we treated SH-SY5Y cells with monomeric form of Aβ. We demonstrated that Aβ significantly increased the phosphorylation of PRAK as well as the interaction between PRAK and RAGE. We showed that knockdown of PRAK rescued mTORC1 inactivation induced by Aβ treatment and decreased the formation of Aβ-induced autophagosome.

Conclusions

We provide evidence that PRAK plays a critical role in AD pathology as a key interactor of RAGE. Thus, our data suggest that PRAK might be a potential therapeutic target of AD involved in RAGE-mediated cell signaling induced by Aβ.
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Metadata
Title
The novel RAGE interactor PRAK is associated with autophagy signaling in Alzheimer’s disease pathogenesis
Authors
Yoonhee Kim
Chaeyoung Kim
Sung Min Son
Hyundong Song
Hyun Seok Hong
Sun-ho Han
Inhee Mook-Jung
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Molecular Neurodegeneration / Issue 1/2016
Electronic ISSN: 1750-1326
DOI
https://doi.org/10.1186/s13024-016-0068-5

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