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

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 pe...

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Autores principales:	Sangwoo Ham, Yun-Il Lee, Minkyung Jo, Hyojung Kim, Hojin Kang, Areum Jo, Gum Hwa Lee, Yun Jeong Mo, Sang Chul Park, Yun Song Lee, Joo-Ho Shin, Yunjong Lee
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/57f98ba85a7143c8bb7feb9bb5391a36
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spelling	oai:doaj.org-article:57f98ba85a7143c8bb7feb9bb5391a362021-12-02T15:05:59ZHydrocortisone-induced parkin prevents dopaminergic cell death via CREB pathway in Parkinson’s disease model10.1038/s41598-017-00614-w2045-2322https://doaj.org/article/57f98ba85a7143c8bb7feb9bb5391a362017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00614-whttps://doaj.org/toc/2045-2322Abstract 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.Sangwoo HamYun-Il LeeMinkyung JoHyojung KimHojin KangAreum JoGum Hwa LeeYun Jeong MoSang Chul ParkYun Song LeeJoo-Ho ShinYunjong LeeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sangwoo Ham Yun-Il Lee Minkyung Jo Hyojung Kim Hojin Kang Areum Jo Gum Hwa Lee Yun Jeong Mo Sang Chul Park Yun Song Lee Joo-Ho Shin Yunjong Lee Hydrocortisone-induced parkin prevents dopaminergic cell death via CREB pathway in Parkinson’s disease model
description	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.
format	article
author	Sangwoo Ham Yun-Il Lee Minkyung Jo Hyojung Kim Hojin Kang Areum Jo Gum Hwa Lee Yun Jeong Mo Sang Chul Park Yun Song Lee Joo-Ho Shin Yunjong Lee
author_facet	Sangwoo Ham Yun-Il Lee Minkyung Jo Hyojung Kim Hojin Kang Areum Jo Gum Hwa Lee Yun Jeong Mo Sang Chul Park Yun Song Lee Joo-Ho Shin Yunjong Lee
author_sort	Sangwoo Ham
title	Hydrocortisone-induced parkin prevents dopaminergic cell death via CREB pathway in Parkinson’s disease model
title_short	Hydrocortisone-induced parkin prevents dopaminergic cell death via CREB pathway in Parkinson’s disease model
title_full	Hydrocortisone-induced parkin prevents dopaminergic cell death via CREB pathway in Parkinson’s disease model
title_fullStr	Hydrocortisone-induced parkin prevents dopaminergic cell death via CREB pathway in Parkinson’s disease model
title_full_unstemmed	Hydrocortisone-induced parkin prevents dopaminergic cell death via CREB pathway in Parkinson’s disease model
title_sort	hydrocortisone-induced parkin prevents dopaminergic cell death via creb pathway in parkinson’s disease model
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/57f98ba85a7143c8bb7feb9bb5391a36
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Hydrocortisone-induced parkin prevents dopaminergic cell death via CREB pathway in Parkinson’s disease model

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