Synuclein impairs trafficking and signaling of BDNF in a mouse model of Parkinson’s disease

Abstract Recent studies have demonstrated that hyperphosphorylation of tau protein plays a role in neuronal toxicities of α-synuclein (ASYN) in neurodegenerative disease such as familial Alzheimer’s disease (AD), dementia with Lewy bodies (DLB) and Parkinson’s disease. Using a transgenic mouse model...

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Autores principales:	Fang Fang, Wanlin Yang, Jazmin B. Florio, Edward Rockenstein, Brian Spencer, Xavier M. Orain, Stephanie X. Dong, Huayan Li, Xuqiao Chen, Kijung Sung, Robert A. Rissman, Eliezer Masliah, Jianqing Ding, Chengbiao Wu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/12c01bf2810f488c9d8ecb8510422e17
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spelling	oai:doaj.org-article:12c01bf2810f488c9d8ecb8510422e172021-12-02T11:40:23ZSynuclein impairs trafficking and signaling of BDNF in a mouse model of Parkinson’s disease10.1038/s41598-017-04232-42045-2322https://doaj.org/article/12c01bf2810f488c9d8ecb8510422e172017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04232-4https://doaj.org/toc/2045-2322Abstract Recent studies have demonstrated that hyperphosphorylation of tau protein plays a role in neuronal toxicities of α-synuclein (ASYN) in neurodegenerative disease such as familial Alzheimer’s disease (AD), dementia with Lewy bodies (DLB) and Parkinson’s disease. Using a transgenic mouse model of Parkinson’s disease (PD) that expresses GFP-ASYN driven by the PDGF-β promoter, we investigated how accumulation of ASYN impacted axonal function. We found that retrograde axonal trafficking of brain-derived neurotrophic factor (BDNF) in DIV7 cultures of E18 cortical neurons was markedly impaired at the embryonic stage, even though hyperphosphorylation of tau was not detectable in these neurons at this stage. Interestingly, we found that overexpressed ASYN interacted with dynein and induced a significant increase in the activated levels of small Rab GTPases such as Rab5 and Rab7, both key regulators of endocytic processes. Furthermore, expression of ASYN resulted in neuronal atrophy in DIV7 cortical cultures of either from E18 transgenic mouse model or from rat E18 embryos that were transiently transfected with ASYN-GFP for 72 hrs. Our studies suggest that excessive ASYN likely alters endocytic pathways leading to axonal dysfunction in embryonic cortical neurons in PD mouse models.Fang FangWanlin YangJazmin B. FlorioEdward RockensteinBrian SpencerXavier M. OrainStephanie X. DongHuayan LiXuqiao ChenKijung SungRobert A. RissmanEliezer MasliahJianqing DingChengbiao WuNature 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 Fang Fang Wanlin Yang Jazmin B. Florio Edward Rockenstein Brian Spencer Xavier M. Orain Stephanie X. Dong Huayan Li Xuqiao Chen Kijung Sung Robert A. Rissman Eliezer Masliah Jianqing Ding Chengbiao Wu Synuclein impairs trafficking and signaling of BDNF in a mouse model of Parkinson’s disease
description	Abstract Recent studies have demonstrated that hyperphosphorylation of tau protein plays a role in neuronal toxicities of α-synuclein (ASYN) in neurodegenerative disease such as familial Alzheimer’s disease (AD), dementia with Lewy bodies (DLB) and Parkinson’s disease. Using a transgenic mouse model of Parkinson’s disease (PD) that expresses GFP-ASYN driven by the PDGF-β promoter, we investigated how accumulation of ASYN impacted axonal function. We found that retrograde axonal trafficking of brain-derived neurotrophic factor (BDNF) in DIV7 cultures of E18 cortical neurons was markedly impaired at the embryonic stage, even though hyperphosphorylation of tau was not detectable in these neurons at this stage. Interestingly, we found that overexpressed ASYN interacted with dynein and induced a significant increase in the activated levels of small Rab GTPases such as Rab5 and Rab7, both key regulators of endocytic processes. Furthermore, expression of ASYN resulted in neuronal atrophy in DIV7 cortical cultures of either from E18 transgenic mouse model or from rat E18 embryos that were transiently transfected with ASYN-GFP for 72 hrs. Our studies suggest that excessive ASYN likely alters endocytic pathways leading to axonal dysfunction in embryonic cortical neurons in PD mouse models.
format	article
author	Fang Fang Wanlin Yang Jazmin B. Florio Edward Rockenstein Brian Spencer Xavier M. Orain Stephanie X. Dong Huayan Li Xuqiao Chen Kijung Sung Robert A. Rissman Eliezer Masliah Jianqing Ding Chengbiao Wu
author_facet	Fang Fang Wanlin Yang Jazmin B. Florio Edward Rockenstein Brian Spencer Xavier M. Orain Stephanie X. Dong Huayan Li Xuqiao Chen Kijung Sung Robert A. Rissman Eliezer Masliah Jianqing Ding Chengbiao Wu
author_sort	Fang Fang
title	Synuclein impairs trafficking and signaling of BDNF in a mouse model of Parkinson’s disease
title_short	Synuclein impairs trafficking and signaling of BDNF in a mouse model of Parkinson’s disease
title_full	Synuclein impairs trafficking and signaling of BDNF in a mouse model of Parkinson’s disease
title_fullStr	Synuclein impairs trafficking and signaling of BDNF in a mouse model of Parkinson’s disease
title_full_unstemmed	Synuclein impairs trafficking and signaling of BDNF in a mouse model of Parkinson’s disease
title_sort	synuclein impairs trafficking and signaling of bdnf in a mouse model of parkinson’s disease
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/12c01bf2810f488c9d8ecb8510422e17
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Synuclein impairs trafficking and signaling of BDNF in a mouse model of Parkinson’s disease

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