Tau Enhances alpha-Synuclein Aggregation and Toxicity in Cellular Models of Synucleinopathy
Por:
Badiola, N, de Oliveira, RM, Herrera, F, Guardia-Laguarta, C, Goncalves, SA, Pera, M, Suarez-Calvet, M, Clarimon, J, Outeiro, TF, Lleo, A
Publicada:
24 oct 2011
Resumen:
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 alpha-synuclein (alpha-syn) aggregates has been described in neurodegenerative disorders with primary deposition of alpha-syn, such as Parkinson's disease and dementia with Lewy bodies. Although it is known that tau and alpha-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 alpha-syn aggregation. Using confocal microscopy and FRET-based techniques we observed that tau colocalized and interacted with alpha-syn aggregates. We also found that tau overexpression changed the pattern of alpha-syn aggregation, reducing the size and increasing the number of aggregates. This shift was accompanied by an increase in the levels of insoluble alpha-syn. Furthermore, co-transfection of tau increased secreted alpha-syn and cytotoxicity.
Conclusions/Significance: Our data suggest that tau enhances alpha-syn aggregation and toxicity and disrupts alpha-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.
Filiaciones:
Badiola, N:
Hosp Santa Creu & Sant Pau, Inst Invest Biomed St Pau, Barcelona, Spain
CIBERNED, Madrid, Spain
de Oliveira, RM:
Inst Mol Med, Cell & Mol Neurosci Unit, Lisbon, Portugal
Herrera, F:
Inst Mol Med, Cell & Mol Neurosci Unit, Lisbon, Portugal
Guardia-Laguarta, C:
Hosp Santa Creu & Sant Pau, Inst Invest Biomed St Pau, Barcelona, Spain
CIBERNED, Madrid, Spain
Goncalves, SA:
Inst Mol Med, Cell & Mol Neurosci Unit, Lisbon, Portugal
Pera, M:
Hosp Santa Creu & Sant Pau, Inst Invest Biomed St Pau, Barcelona, Spain
CIBERNED, Madrid, Spain
Suarez-Calvet, M:
Hosp Santa Creu & Sant Pau, Inst Invest Biomed St Pau, Barcelona, Spain
CIBERNED, Madrid, Spain
Clarimon, J:
Hosp Santa Creu & Sant Pau, Inst Invest Biomed St Pau, Barcelona, Spain
CIBERNED, Madrid, Spain
Outeiro, TF:
Inst Mol Med, Cell & Mol Neurosci Unit, Lisbon, Portugal
Univ Lisbon, Fac Med, P-1699 Lisbon, Portugal
Lleo, A:
Hosp Santa Creu & Sant Pau, Inst Invest Biomed St Pau, Barcelona, Spain
CIBERNED, Madrid, Spain
Gold, Green Published
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