Tau enhances α-synuclein aggregation and toxicity in cellular models of synucleinopathy.
<h4>Background</h4>The simultaneous accumulation of different misfolded proteins in the central nervous system is a common feature in many neurodegenerative diseases. In most cases, co-occurrence of abnormal deposited proteins is observed in different brain regions and cell populations,...
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2011
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oai:doaj.org-article:b383f4ea139f4787b85f88b1e9deb2c42021-11-18T07:35:52ZTau enhances α-synuclein aggregation and toxicity in cellular models of synucleinopathy.1932-620310.1371/journal.pone.0026609https://doaj.org/article/b383f4ea139f4787b85f88b1e9deb2c42011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22039514/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>The simultaneous accumulation of different misfolded proteins in the central nervous system is a common feature in many neurodegenerative diseases. In most cases, co-occurrence of abnormal deposited proteins is observed in different brain regions and cell populations, but, in some instances, the proteins can be found in the same cellular aggregates. Co-occurrence of tau and α-synuclein (α-syn) aggregates has been described in neurodegenerative disorders with primary deposition of α-syn, such as Parkinson's disease and dementia with Lewy bodies. Although it is known that tau and α-syn have pathological synergistic effects on their mutual fibrillization, the underlying biological effects remain unclear.<h4>Methodology/principal findings</h4>We used different cell models of synucleinopathy to investigate the effects of tau on α-syn aggregation. Using confocal microscopy and FRET-based techniques we observed that tau colocalized and interacted with α-syn aggregates. We also found that tau overexpression changed the pattern of α-syn aggregation, reducing the size and increasing the number of aggregates. This shift was accompanied by an increase in the levels of insoluble α-syn. Furthermore, co-transfection of tau increased secreted α-syn and cytotoxicity.<h4>Conclusions/significance</h4>Our data suggest that tau enhances α-syn aggregation and toxicity and disrupts α-syn inclusion formation. This pathological synergistic effect between tau and α-syn may amplify the deleterious process and spread the damage in neurodegenerative diseases that show co-occurrence of both pathologies.Nahuai BadiolaRita Machado de OliveiraFederico HerreraCristina Guardia-LaguartaSusana A GonçalvesMarta PeraMarc Suárez-CalvetJordi ClarimonTiago Fleming OuteiroAlberto LleóPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 10, p e26609 (2011) |
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Medicine R Science Q Nahuai Badiola Rita Machado de Oliveira Federico Herrera Cristina Guardia-Laguarta Susana A Gonçalves Marta Pera Marc Suárez-Calvet Jordi Clarimon Tiago Fleming Outeiro Alberto Lleó Tau enhances α-synuclein aggregation and toxicity in cellular models of synucleinopathy. |
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<h4>Background</h4>The simultaneous accumulation of different misfolded proteins in the central nervous system is a common feature in many neurodegenerative diseases. In most cases, co-occurrence of abnormal deposited proteins is observed in different brain regions and cell populations, but, in some instances, the proteins can be found in the same cellular aggregates. Co-occurrence of tau and α-synuclein (α-syn) aggregates has been described in neurodegenerative disorders with primary deposition of α-syn, such as Parkinson's disease and dementia with Lewy bodies. Although it is known that tau and α-syn have pathological synergistic effects on their mutual fibrillization, the underlying biological effects remain unclear.<h4>Methodology/principal findings</h4>We used different cell models of synucleinopathy to investigate the effects of tau on α-syn aggregation. Using confocal microscopy and FRET-based techniques we observed that tau colocalized and interacted with α-syn aggregates. We also found that tau overexpression changed the pattern of α-syn aggregation, reducing the size and increasing the number of aggregates. This shift was accompanied by an increase in the levels of insoluble α-syn. Furthermore, co-transfection of tau increased secreted α-syn and cytotoxicity.<h4>Conclusions/significance</h4>Our data suggest that tau enhances α-syn aggregation and toxicity and disrupts α-syn inclusion formation. This pathological synergistic effect between tau and α-syn may amplify the deleterious process and spread the damage in neurodegenerative diseases that show co-occurrence of both pathologies. |
format |
article |
author |
Nahuai Badiola Rita Machado de Oliveira Federico Herrera Cristina Guardia-Laguarta Susana A Gonçalves Marta Pera Marc Suárez-Calvet Jordi Clarimon Tiago Fleming Outeiro Alberto Lleó |
author_facet |
Nahuai Badiola Rita Machado de Oliveira Federico Herrera Cristina Guardia-Laguarta Susana A Gonçalves Marta Pera Marc Suárez-Calvet Jordi Clarimon Tiago Fleming Outeiro Alberto Lleó |
author_sort |
Nahuai Badiola |
title |
Tau enhances α-synuclein aggregation and toxicity in cellular models of synucleinopathy. |
title_short |
Tau enhances α-synuclein aggregation and toxicity in cellular models of synucleinopathy. |
title_full |
Tau enhances α-synuclein aggregation and toxicity in cellular models of synucleinopathy. |
title_fullStr |
Tau enhances α-synuclein aggregation and toxicity in cellular models of synucleinopathy. |
title_full_unstemmed |
Tau enhances α-synuclein aggregation and toxicity in cellular models of synucleinopathy. |
title_sort |
tau enhances α-synuclein aggregation and toxicity in cellular models of synucleinopathy. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2011 |
url |
https://doaj.org/article/b383f4ea139f4787b85f88b1e9deb2c4 |
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