title: The novel RAGE interactor PRAK is associated with autophagy signaling in Alzheimer's disease pathogenesis.
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.
authors.affiliation: Department of Biochemistry and Biomedical Sciences, Seoul National University College of Medicine, 103 Daehak-ro, Jongro-gu, Seoul, 110-799, Korea. unihoi@snu.ac.kr.
authors.forename: Yoonhee
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Biochemistry and Biomedical Sciences, Seoul National University College of Medicine, 103 Daehak-ro, Jongro-gu, Seoul, 110-799, Korea. Kim.Chaeyoung@mayo.edu.
authors.forename: Chaeyoung
authors.initials: C
authors.lastname: Kim
authors.affiliation: Department of Biochemistry and Biomedical Sciences, Seoul National University College of Medicine, 103 Daehak-ro, Jongro-gu, Seoul, 110-799, Korea. sonsm119@snu.ac.kr.
authors.forename: Sung Min
authors.initials: SM
authors.lastname: Son
authors.affiliation: Department of Biochemistry and Biomedical Sciences, Seoul National University College of Medicine, 103 Daehak-ro, Jongro-gu, Seoul, 110-799, Korea. eternalshd@snu.ac.kr.
authors.forename: Hyundong
authors.initials: H
authors.lastname: Song
authors.affiliation: Department of Biochemistry and Biomedical Sciences, Seoul National University College of Medicine, 103 Daehak-ro, Jongro-gu, Seoul, 110-799, Korea. hshong@medifron.com.
authors.forename: Hyun Seok
authors.initials: HS
authors.lastname: Hong
authors.affiliation: Department of Biochemistry and Biomedical Sciences, Seoul National University College of Medicine, 103 Daehak-ro, Jongro-gu, Seoul, 110-799, Korea. sunho@snu.ac.kr.
authors.forename: Sun-ho
authors.initials: SH
authors.lastname: Han
authors.affiliation: Department of Biochemistry and Biomedical Sciences, Seoul National University College of Medicine, 103 Daehak-ro, Jongro-gu, Seoul, 110-799, Korea. inhee@snu.ac.kr.
authors.forename: Inhee
authors.initials: I
authors.lastname: Mook-Jung
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001343:Autophagy / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D016229:Amyloid beta-Peptides; D047908:Intracellular Signaling Peptides and Proteins; D000067759:Receptor for Advanced Glycation End Products; C111049:MAP-kinase-activated kinase 5; D017346:Protein Serine-Threonine Kinases