國家衛生研究院 NHRI:Item 3990099045/10559
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/10559


    Title: Tat-haFGF14-154 upregulates ADAM10 to attenuate the alzheimer phenotype of APP/PS1 mice through the PI3K-CREB-IRE1alpha/XBP1 pathway
    Other Titles: Tat-haFGF14-154 Upregulates ADAM10 to Attenuate the Alzheimer Phenotype of APP/PS1 Mice through the PI3K-CREB-IRE1a/XBP1 Pathway
    Authors: Meng, T;Cao, Q;Lei, P;Bush, AI;Xiang, Q;Su, Z;He, X;Rogers, JT;Chiu, IM;Zhang, Q;Huang, Y
    Contributors: Institute of Cellular and Systems Medicine
    Abstract: Acid fibroblast growth factor (aFGF) has shown neuroprotection in Alzheimer's disease (AD) models in previous studies, yet its mechanism is still uncertain. Here we report that the efficacy of Tat-haFGF14-154 is markedly increased when loaded cationic liposomes for intranasal delivery are intranasally administered to APP/PS1 mice. Our results demonstrated that liposomal Tat-haFGF14-154 treatment significantly ameliorated behavioral deficits, relieved brain Abeta burden, and increased the expression and activity of disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) in the brain. Tat-haFGF14-154 antagonized Abeta1-42-induced cell death and structural damage in rat primary neurons in an ADAM10-dependent manner, which, in turn, was promoted by the activation of XBP1 splicing and modulated by the PI3K-CREB pathway. Both knockdown of ADAM10 and inhibition of PI3K (LY294002) negated Tat-haFGF14-154 rescue. Thus, Tat-haFGF14-154 activates the IRE1alpha/XBP1 pathway of the unfolded protein response (UPR) against the endoplasmic reticulum (ER) stress induced by Abeta, and, subsequently, the nuclear translocation of spliced XBP1 (XBP1s) promotes transcription of ADAM10. These results highlight the important role of ADAM10 and its activation through the PI3K-CREB-IRE1alpha/XBP1 pathway as a key factor in the mechanism of neuroprotection for Tat-haFGF14-154.
    Date: 2017-06-16
    Relation: Molecular Therapy. Nucleic Acids. 2017 Jun 16;7:439-452.
    Link to: http://dx.doi.org/10.1016/j.omtn.2017.05.004
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2162-2531&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000402193600002
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85020491869
    Appears in Collections:[Ing-Ming Chiu] Periodical Articles

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