Tau enhances α-synuclein aggregation and toxicity in cellular models of synucleinopathy
Badiola Benito, Nahuai (Institut d'Investigació Biomèdica Sant Pau)
de Oliveira, Rita Machado (Institut d'Investigació Biomèdica Sant Pau)
Herrera, Federico (Institut d'Investigació Biomèdica Sant Pau)
Guardia-Laguarta, Cristina (Institut d'Investigació Biomèdica Sant Pau)
Gonçalves, Susana A. (Institut d'Investigació Biomèdica Sant Pau)
Pera, Marta (Institut d'Investigació Biomèdica Sant Pau)
Suárez-Calvet, Marc (Institut d'Investigació Biomèdica Sant Pau)
Clarimón, Jordi (Institut d'Investigació Biomèdica Sant Pau)
Outeiro, Tiago Fleming (Faculdade de Medicina da Universidade de Lisboa)
Lleó, Alberto (Institut d'Investigació Biomèdica Sant Pau)
Universitat Autònoma de Barcelona

Date:	2011
Abstract:	Background: 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. Methodology/Principal Findings: 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. Conclusions/Significance: 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. © 2011 Badiola et al.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	PloS one, Vol. 6 Núm. 10 (24 2011) , p. e26609, ISSN 1932-6203

DOI: 10.1371/journal.pone.0026609
PMID: 22039514

9 p, 493.3 KB

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