title: Tau enhances α-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 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.
  
  
  RESULTS
  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
  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.
authors: Instituto de Investigacions Biomediques Sant Pau, Hospital de Sant Pau, Barcelona, Spain.
authors: Nahuai
authors: N
authors: Badiola
authors: Rita Machado
authors: RM
authors: de Oliveira
authors: Federico
authors: F
authors: Herrera
authors: Cristina
authors: C
authors: Guardia-Laguarta
authors: Susana A
authors: SA
authors: Gonçalves
authors: Marta
authors: M
authors: Pera
authors: Marc
authors: M
authors: Suárez-Calvet
authors: Jordi
authors: J
authors: Clarimon
authors: Tiago Fleming
authors: TF
authors: Outeiro
authors: Alberto
authors: A
authors: Lleó
mesh_terms: D015153:Blotting, Western; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D018613:Microscopy, Confocal; D008954:Models, Biological; D008970:Molecular Weight; D051844:alpha-Synuclein / Q000096:biosynthesis / Q000378:metabolism* / Q000633:toxicity; D016875:tau Proteins / Q000502:physiology*
chemical_list: D051844:alpha-Synuclein; D016875:tau Proteins