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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/11293


    Title: Post-treatment with PT302, a long-acting Exendin-4 sustained release formulation, reduces dopaminergic neurodegeneration in a 6-Hydroxydopamine rat model of Parkinson's disease
    Authors: Chen, S;Yu, SJ;Li, Y;Lecca, D;Glotfelty, E;Kim, HK;Choi, HI;Hoffer, BJ;Greig, NH;Kim, DS;Wang, Y
    Contributors: Center for Neuropsychiatric Research
    Abstract: We previously demonstrated that pretreatment with Exendin-4, a glucagon-like peptide-1 (GLP-1) receptor agonist, reduces 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) -mediated dopaminergic neurodegeneration. The use of GLP-1 or Exendin-4 for Parkinson's disease (PD) patients is limited by their short half-lives. The purpose of this study was to evaluate a new extended release Exendin-4 formulation, PT302, in a rat model of PD. Subcutaneous administration of PT302 resulted in sustained elevations of Exendin-4 in plasma for >20 days in adult rats. To define an efficacious dose within this range, rats were administered PT302 once every 2 weeks either before or following the unilaterally 6-hydroxydopamine lesioning. Pre- and post-treatment with PT302 significantly reduced methamphetamine-induced rotation after lesioning. For animals given PT302 post lesion, blood and brain samples were collected on day 47 for measurements of plasma Exendin-4 levels and brain tyrosine hydroxylase immunoreactivity (TH-IR). PT302 significantly increased TH-IR in the lesioned substantia nigra and striatum. There was a significant correlation between plasma Exendin-4 levels and TH-IR in the substantia nigra and striatum on the lesioned side. Our data suggest that post-treatment with PT302 provides long-lasting Exendin-4 release and reduces neurodegeneration of nigrostriatal dopaminergic neurons in a 6-hydroxydopamine rat model of PD at a clinically relevant dose.
    Date: 2018-07-16
    Relation: Scientific Reports. 2018 Jul 16;8:Article number 10722.
    Link to: http://dx.doi.org/10.1038/s41598-018-28449-z
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2045-2322&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000438679100027
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85050390228
    Appears in Collections:[王昀] 期刊論文
    [劉誠珍] 期刊論文

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