Activators of alpha synuclein expression identified by reporter cell line-based high throughput drug screen

Abstract Multiplications, mutations and dysregulation of the alpha synuclein gene (SNCA) are associated with the demise of dopaminergic neurons and are considered to play important roles in the pathogenesis of familial and sporadic forms of Parkinson’s disease. Regulation of SNCA expression might th...

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Autores principales:	Fabian Stahl, Philip Denner, Dominik Piston, Bernd O. Evert, Laura de Boni, Ina Schmitt, Peter Breuer, Ullrich Wüllner
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/35e23d580f6a483d801a8bf67c002435
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spelling	oai:doaj.org-article:35e23d580f6a483d801a8bf67c0024352021-12-02T18:37:11ZActivators of alpha synuclein expression identified by reporter cell line-based high throughput drug screen10.1038/s41598-021-98841-92045-2322https://doaj.org/article/35e23d580f6a483d801a8bf67c0024352021-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98841-9https://doaj.org/toc/2045-2322Abstract Multiplications, mutations and dysregulation of the alpha synuclein gene (SNCA) are associated with the demise of dopaminergic neurons and are considered to play important roles in the pathogenesis of familial and sporadic forms of Parkinson’s disease. Regulation of SNCA expression might thus be an appropriate target for treatment. We aimed to identify specific modulators of SNCA transcription, generated CRISPR/Cas9 modified SNCA-GFP-luciferase (LUC) genomic fusion- and control cell lines and screened a library of 1649 bioactive compounds, including the FDA approved drugs. We found no inhibitors but three selective activators which increased SNCA mRNA and protein levels.Fabian StahlPhilip DennerDominik PistonBernd O. EvertLaura de BoniIna SchmittPeter BreuerUllrich WüllnerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Fabian Stahl Philip Denner Dominik Piston Bernd O. Evert Laura de Boni Ina Schmitt Peter Breuer Ullrich Wüllner Activators of alpha synuclein expression identified by reporter cell line-based high throughput drug screen
description	Abstract Multiplications, mutations and dysregulation of the alpha synuclein gene (SNCA) are associated with the demise of dopaminergic neurons and are considered to play important roles in the pathogenesis of familial and sporadic forms of Parkinson’s disease. Regulation of SNCA expression might thus be an appropriate target for treatment. We aimed to identify specific modulators of SNCA transcription, generated CRISPR/Cas9 modified SNCA-GFP-luciferase (LUC) genomic fusion- and control cell lines and screened a library of 1649 bioactive compounds, including the FDA approved drugs. We found no inhibitors but three selective activators which increased SNCA mRNA and protein levels.
format	article
author	Fabian Stahl Philip Denner Dominik Piston Bernd O. Evert Laura de Boni Ina Schmitt Peter Breuer Ullrich Wüllner
author_facet	Fabian Stahl Philip Denner Dominik Piston Bernd O. Evert Laura de Boni Ina Schmitt Peter Breuer Ullrich Wüllner
author_sort	Fabian Stahl
title	Activators of alpha synuclein expression identified by reporter cell line-based high throughput drug screen
title_short	Activators of alpha synuclein expression identified by reporter cell line-based high throughput drug screen
title_full	Activators of alpha synuclein expression identified by reporter cell line-based high throughput drug screen
title_fullStr	Activators of alpha synuclein expression identified by reporter cell line-based high throughput drug screen
title_full_unstemmed	Activators of alpha synuclein expression identified by reporter cell line-based high throughput drug screen
title_sort	activators of alpha synuclein expression identified by reporter cell line-based high throughput drug screen
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/35e23d580f6a483d801a8bf67c002435
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Activators of alpha synuclein expression identified by reporter cell line-based high throughput drug screen

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