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Hydrocortisone-induced parkin prevents dopaminergic cell death via CREB pathway in Parkinson's disease model

Title
Hydrocortisone-induced parkin prevents dopaminergic cell death via CREB pathway in Parkinson's disease model
Author(s)
Ham, SangwooLee, Yun-IlJo, MinkyungKim, HyojungKang, HojinJo, AreumLee, Gum HwaMo, Yun JeongPark, Sang ChulLee, Yun SongShin, Joo-HoLee, Yunjong
Issued Date
2017-04
Citation
Scientific Reports, v.7, no.1
Type
Article
Keywords
2 PartsAlpha SynucleinApoptosisER StressGeneGlucocorticoidsMouse ModelProtective FunctionReceptorUbiquitination
ISSN
2045-2322
Abstract
Dysfunctional parkin due to mutations or post-translational modifications contributes to dopaminergic neurodegeneration in Parkinson's disease (PD). Overexpression of parkin provides protection against cellular stresses and prevents dopamine cell loss in several PD animal models. Here we performed an unbiased high-throughput luciferase screening to identify chemicals that can increase parkin expression. Among promising parkin inducers, hydrocortisone possessed the most favorable profiles including parkin induction ability, cell protection ability, and physicochemical property of absorption, distribution, metabolism, and excretion (ADME) without inducing endoplasmic reticulum stress. We found that hydrocortisone-induced parkin expression was accountable for cell protection against oxidative stress. Hydrocortisone-activated parkin expression was mediated by CREB pathway since gRNA to CREB abolished hydrocortisone's ability to induce parkin. Finally, hydrocortisone treatment in mice increased brain parkin levels and prevented 6-hydroxy dopamine induced dopamine cell loss when assessed at 4 days after the toxin's injection. Our results showed that hydrocortisone could stimulate parkin expression via CREB pathway and the induced parkin expression was accountable for its neuroprotective effect. Since glucocorticoid is a physiological hormone, maintaining optimal levels of glucocorticoid might be a potential therapeutic or preventive strategy for Parkinson's disease. © 2017 The Author(s).
URI
http://hdl.handle.net/20.500.11750/4200
DOI
10.1038/s41598-017-00614-w
Publisher
Nature Publishing Group
Related Researcher
Files in This Item:
10.1038_s41598_017_00614_w.pdf

10.1038_s41598_017_00614_w.pdf

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Appears in Collections:
Division of Biotechnology 1. Journal Articles

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