期刊
PLOS ONE
卷 6, 期 10, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0026609
关键词
-
资金
- Ministerio de Ciencia e Innovacion [FISPI071137]
- Fundacio Marato TV3 [072610]
- Centro Investigacion Biomedica en Red Enfermedades Neurodegenerativas (CIBERNED)
- Marie Curie International Reintegration Grant (Neurofold)
- EMBO
- Fundacao para a Ciencia e a Tecnologia [SFRH/BPD/41416/2007, SFRH/BPD/63530/2009]
- Fundação para a Ciência e a Tecnologia [SFRH/BPD/41416/2007] Funding Source: FCT
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据