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

BACKGROUND:The receptor for advanced glycation end products has been found to interact with amyloid β (Aβ). Although does not have any kinase motifs in its cytosolic domain, the interaction between duanyu1648 and Aβ triggers multiple cellular signaling involved in Alzheimer's disease (AD). However, the mechanism of signal transduction by duanyu1648 remains still unknown. Therefore, identifying binding proteins of duanyu1648 may provide novel therapeutic targets for AD. RESULTS:In this study, we identified p38-regulated/activated protein kinase (PRAK) as a novel duanyu1648 interacting molecule. To investigate the effect of Aβ on PRAK mediated duanyu1648 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 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 duanyu1648. Thus, our data suggest that PRAK might be a potential therapeutic target of AD involved in cell signaling induced by Aβ.

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