Novel animal model defines genetic contributions for neuron-to-neuron transfer of α-synuclein

Abstract Cell-to-cell spreading of misfolded α-synuclein (α-syn) is suggested to contribute to the progression of neuropathology in Parkinson’s disease (PD). Compelling evidence supports the hypothesis that misfolded α-syn transmits from neuron-to-neuron and seeds aggregation of the protein in the r...

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Autores principales:	Trevor Tyson, Megan Senchuk, Jason F. Cooper, Sonia George, Jeremy M. Van Raamsdonk, Patrik Brundin
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e44c58a75bc5424cab532651a38f2161
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spelling	oai:doaj.org-article:e44c58a75bc5424cab532651a38f21612021-12-02T12:32:16ZNovel animal model defines genetic contributions for neuron-to-neuron transfer of α-synuclein10.1038/s41598-017-07383-62045-2322https://doaj.org/article/e44c58a75bc5424cab532651a38f21612017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07383-6https://doaj.org/toc/2045-2322Abstract Cell-to-cell spreading of misfolded α-synuclein (α-syn) is suggested to contribute to the progression of neuropathology in Parkinson’s disease (PD). Compelling evidence supports the hypothesis that misfolded α-syn transmits from neuron-to-neuron and seeds aggregation of the protein in the recipient cells. Furthermore, α-syn frequently appears to propagate in the brains of PD patients following a stereotypic pattern consistent with progressive spreading along anatomical pathways. We have generated a C. elegans model that mirrors this progression and allows us to monitor α-syn neuron-to-neuron transmission in a live animal over its lifespan. We found that modulation of autophagy or exo/endocytosis, affects α-syn transfer. Furthermore, we demonstrate that silencing C. elegans orthologs of PD-related genes also increases the accumulation of α-syn. This novel worm model is ideal for screening molecules and genes to identify those that modulate prion-like spreading of α-syn in order to target novel strategies for disease modification in PD and other synucleinopathies.Trevor TysonMegan SenchukJason F. CooperSonia GeorgeJeremy M. Van RaamsdonkPatrik BrundinNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Trevor Tyson Megan Senchuk Jason F. Cooper Sonia George Jeremy M. Van Raamsdonk Patrik Brundin Novel animal model defines genetic contributions for neuron-to-neuron transfer of α-synuclein
description	Abstract Cell-to-cell spreading of misfolded α-synuclein (α-syn) is suggested to contribute to the progression of neuropathology in Parkinson’s disease (PD). Compelling evidence supports the hypothesis that misfolded α-syn transmits from neuron-to-neuron and seeds aggregation of the protein in the recipient cells. Furthermore, α-syn frequently appears to propagate in the brains of PD patients following a stereotypic pattern consistent with progressive spreading along anatomical pathways. We have generated a C. elegans model that mirrors this progression and allows us to monitor α-syn neuron-to-neuron transmission in a live animal over its lifespan. We found that modulation of autophagy or exo/endocytosis, affects α-syn transfer. Furthermore, we demonstrate that silencing C. elegans orthologs of PD-related genes also increases the accumulation of α-syn. This novel worm model is ideal for screening molecules and genes to identify those that modulate prion-like spreading of α-syn in order to target novel strategies for disease modification in PD and other synucleinopathies.
format	article
author	Trevor Tyson Megan Senchuk Jason F. Cooper Sonia George Jeremy M. Van Raamsdonk Patrik Brundin
author_facet	Trevor Tyson Megan Senchuk Jason F. Cooper Sonia George Jeremy M. Van Raamsdonk Patrik Brundin
author_sort	Trevor Tyson
title	Novel animal model defines genetic contributions for neuron-to-neuron transfer of α-synuclein
title_short	Novel animal model defines genetic contributions for neuron-to-neuron transfer of α-synuclein
title_full	Novel animal model defines genetic contributions for neuron-to-neuron transfer of α-synuclein
title_fullStr	Novel animal model defines genetic contributions for neuron-to-neuron transfer of α-synuclein
title_full_unstemmed	Novel animal model defines genetic contributions for neuron-to-neuron transfer of α-synuclein
title_sort	novel animal model defines genetic contributions for neuron-to-neuron transfer of α-synuclein
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/e44c58a75bc5424cab532651a38f2161
work_keys_str_mv	AT trevortyson novelanimalmodeldefinesgeneticcontributionsforneurontoneurontransferofasynuclein AT megansenchuk novelanimalmodeldefinesgeneticcontributionsforneurontoneurontransferofasynuclein AT jasonfcooper novelanimalmodeldefinesgeneticcontributionsforneurontoneurontransferofasynuclein AT soniageorge novelanimalmodeldefinesgeneticcontributionsforneurontoneurontransferofasynuclein AT jeremymvanraamsdonk novelanimalmodeldefinesgeneticcontributionsforneurontoneurontransferofasynuclein AT patrikbrundin novelanimalmodeldefinesgeneticcontributionsforneurontoneurontransferofasynuclein
_version_	1718394128290545664

Novel animal model defines genetic contributions for neuron-to-neuron transfer of α-synuclein

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