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

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 Parki...

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Autores principales: Fang, Fang, Yang, Wanlin, Florio, Jazmin B., Rockenstein, Edward, Spencer, Brian, Orain, Xavier M., Dong, Stephanie X., Li, Huayan, Chen, Xuqiao, Sung, Kijung, Rissman, Robert A., Masliah, Eliezer, Ding, Jianqing, Wu, Chengbiao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5478665/
https://www.ncbi.nlm.nih.gov/pubmed/28634349
http://dx.doi.org/10.1038/s41598-017-04232-4
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author Fang, Fang
Yang, Wanlin
Florio, Jazmin B.
Rockenstein, Edward
Spencer, Brian
Orain, Xavier M.
Dong, Stephanie X.
Li, Huayan
Chen, Xuqiao
Sung, Kijung
Rissman, Robert A.
Masliah, Eliezer
Ding, Jianqing
Wu, Chengbiao
author_facet Fang, Fang
Yang, Wanlin
Florio, Jazmin B.
Rockenstein, Edward
Spencer, Brian
Orain, Xavier M.
Dong, Stephanie X.
Li, Huayan
Chen, Xuqiao
Sung, Kijung
Rissman, Robert A.
Masliah, Eliezer
Ding, Jianqing
Wu, Chengbiao
author_sort Fang, Fang
collection PubMed
description 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.
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spelling pubmed-54786652017-06-23 Synuclein impairs trafficking and signaling of BDNF in a mouse model of Parkinson’s disease Fang, Fang Yang, Wanlin Florio, Jazmin B. Rockenstein, Edward Spencer, Brian Orain, Xavier M. Dong, Stephanie X. Li, Huayan Chen, Xuqiao Sung, Kijung Rissman, Robert A. Masliah, Eliezer Ding, Jianqing Wu, Chengbiao Sci Rep Article 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. Nature Publishing Group UK 2017-06-20 /pmc/articles/PMC5478665/ /pubmed/28634349 http://dx.doi.org/10.1038/s41598-017-04232-4 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Fang, Fang
Yang, Wanlin
Florio, Jazmin B.
Rockenstein, Edward
Spencer, Brian
Orain, Xavier M.
Dong, Stephanie X.
Li, Huayan
Chen, Xuqiao
Sung, Kijung
Rissman, Robert A.
Masliah, Eliezer
Ding, Jianqing
Wu, Chengbiao
Synuclein impairs trafficking and signaling of BDNF in a mouse model of Parkinson’s disease
title 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_short 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5478665/
https://www.ncbi.nlm.nih.gov/pubmed/28634349
http://dx.doi.org/10.1038/s41598-017-04232-4
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