Dataset Information

Tau enhances ?-synuclein aggregation and toxicity in cellular models of synucleinopathy.

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 ?-synuclein (?-syn) aggregates has been described in neurodegenerative disorders with primary deposition of ?-syn, such as Parkinson's disease and dementia with Lewy bodies. Although it is known that tau and ?-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 ?-syn aggregation. Using confocal microscopy and FRET-based techniques we observed that tau colocalized and interacted with ?-syn aggregates. We also found that tau overexpression changed the pattern of ?-syn aggregation, reducing the size and increasing the number of aggregates. This shift was accompanied by an increase in the levels of insoluble ?-syn. Furthermore, co-transfection of tau increased secreted ?-syn and cytotoxicity.

Conclusions/significance

Our data suggest that tau enhances ?-syn aggregation and toxicity and disrupts ?-syn inclusion formation. This pathological synergistic effect between tau and ?-syn may amplify the deleterious process and spread the damage in neurodegenerative diseases that show co-occurrence of both pathologies.

SUBMITTER: Badiola N

PROVIDER: S-EPMC3200341 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Publications

Tau enhances α-synuclein aggregation and toxicity in cellular models of synucleinopathy.

Badiola Nahuai N de Oliveira Rita Machado RM Herrera Federico F Guardia-Laguarta Cristina C Gonçalves Susana A SA Pera Marta M Suárez-Calvet Marc M Clarimon Jordi J Outeiro Tiago Fleming TF Lleó Alberto A

PloS one 20111024 10

<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 ...[more]

PMID: 22039514

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