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

  • Badiola N
  • de Oliveira R
  • Herrera F
 et al. 
  • 71


    Mendeley users who have this article in their library.
  • 0


    Citations of this article.


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.

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document


  • Nahuai Badiola

  • Rita Machado de Oliveira

  • Cristina Guardia-Laguarta

  • Susana A. Gonçalves

  • Marta Pera

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free