Microtubule depolymerization potentiates alpha-synuclein oligomerization
Microtubule depolymerization potentiates alpha-synuclein oligomerization
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DOI：
10.3389/neuro.24.005.2009
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发表时间：
2010-01-04
影响因子：
4.8
通讯作者：
Cardoso, Sandra M.
中科院分区：
文献类型：
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作者：
Esteves, A. Raquel;Arduino, Daniela M.;Cardoso, Sandra M.
帕金森病（PD）与线粒体功能紊乱和α-突触核蛋白纤维化有关。我们评估了线粒体功能障碍和α-突触核蛋白聚集之间的潜在机制联系。我们研究了一种PD胞质杂交（胞质杂交）细胞系，其中将来自PD受试者的血小板线粒体转移到之前耗尽内源性线粒体DNA的NT 2神经元细胞中。与对照胞质杂交体细胞系相比，PD系显示出降低的ATP水平、增加的游离/聚合微管蛋白比率和α-突触核蛋白寡聚体积累。紫杉醇（稳定微管）使PD微管蛋白比率正常化并减少α-突触核蛋白寡聚化。线粒体功能、细胞骨架稳态和α-突触核蛋白寡聚化之间存在联系。在我们的模型中，线粒体功能障碍触发了游离微管蛋白的增加，从而使微管网络不稳定并促进α-突触核蛋白寡聚化。
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.