期刊
FRONTIERS IN AGING NEUROSCIENCE
卷 1, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/neuro.24.005.2009
关键词
Parkinson disease; cybrids; ATP; alpha-synuclein; tubulin; mitochondria
资金
- Fundacao para a Ciencia e a Tecnologia, Portugal [SFRH/BD/32470/2006]
- GAPI of Faculdade de Medicina da Universidade de Coimbra, Portugal
- Parkinson's Disease Foundation of the Heartland (USA)
- Fundação para a Ciência e a Tecnologia [SFRH/BD/32470/2006] Funding Source: FCT
Parkinson's disease (PD) is associated with perturbed mitochondria function and alpha-synuclein fibrillization. We evaluated potential mechanistic links between mitochondrial dysfunction and alpha-synuclein aggregation. We studied a PD cytoplasmic hybrid (cybrid) cell line in which platelet mitochondria from a PD subject were transferred to NT2 neuronal cells previously depleted of endogenous mitochondrial DNA. Compared to a control cybrid cell line, the PD line showed reduced ATP levels, an increased free/polymerized tubulin ratio, and alpha-synuclein oligomer accumulation. Taxol (which stabilizes microtubules) normalized the PD tubulin ratio and reduced alpha-synuclein oligomerization. A nexus exists between mitochondrial function, cytoskeleton homeostasis, and alpha-synuclein oligomerization. In our model, mitochondrial dysfunction triggers an increased free tubulin, which destabilizes the microtubular network and promotes alpha-synuclein oligomerization.
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