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,...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: 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
Formato: article
Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2011
Materias:
R
Q
Acceso en línea:https://doaj.org/article/b383f4ea139f4787b85f88b1e9deb2c4
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:b383f4ea139f4787b85f88b1e9deb2c4
record_format dspace
spelling 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)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle 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.
description <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
work_keys_str_mv AT nahuaibadiola tauenhancesasynucleinaggregationandtoxicityincellularmodelsofsynucleinopathy
AT ritamachadodeoliveira tauenhancesasynucleinaggregationandtoxicityincellularmodelsofsynucleinopathy
AT federicoherrera tauenhancesasynucleinaggregationandtoxicityincellularmodelsofsynucleinopathy
AT cristinaguardialaguarta tauenhancesasynucleinaggregationandtoxicityincellularmodelsofsynucleinopathy
AT susanaagoncalves tauenhancesasynucleinaggregationandtoxicityincellularmodelsofsynucleinopathy
AT martapera tauenhancesasynucleinaggregationandtoxicityincellularmodelsofsynucleinopathy
AT marcsuarezcalvet tauenhancesasynucleinaggregationandtoxicityincellularmodelsofsynucleinopathy
AT jordiclarimon tauenhancesasynucleinaggregationandtoxicityincellularmodelsofsynucleinopathy
AT tiagoflemingouteiro tauenhancesasynucleinaggregationandtoxicityincellularmodelsofsynucleinopathy
AT albertolleo tauenhancesasynucleinaggregationandtoxicityincellularmodelsofsynucleinopathy
_version_ 1718423244770377728