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

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Authors
Kim, Yoonhee; Kim, Chaeyoung; Son, Sung Min; Song, Hyundong; Hong, Hyun Seok; Han, Sun-ho; Mook-Jung, Inhee
Issue Date
2016-01-12
Publisher
BioMed Central
Citation
Molecular Neurodegeneration, 11(1):4
Keywords
PRAKRAGEAlzheimer’s diseaseAutophagy
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.
Language
English
URI
http://hdl.handle.net/10371/109842
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Biochemistry & Molecular Biology (생화학교실)Journal Papers (저널논문_생화학교실)
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