Department of Biosciences, Università degli Studi di Milano, Milan, Italy.
Sci Rep. 2013;3:1837. doi: 10.1038/srep01837.
The role of microtubule (MT) dysfunction in Parkinson's disease is emerging. It is still unknown whether it is a cause or a consequence of neurodegeneration. Our objective was to assess whether alterations of MT stability precede or follow axonal transport impairment and neurite degeneration in experimental parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in C57Bl mice. MPTP induced a time- and dose-dependent increase in fibres with altered mitochondria distribution, and early changes in cytoskeletal proteins and MT stability. Indeed, we observed significant increases in neuron-specific βIII tubulin and enrichment of deTyr tubulin in dopaminergic neurons. Finally, we showed that repeated daily administrations of the MT stabilizer Epothilone D rescued MT defects and attenuated nigrostriatal degeneration induced by MPTP. These data suggest that alteration of ΜΤs is an early event specifically associated with dopaminergic neuron degeneration. Pharmacological stabilization of MTs may be a viable strategy for the management of parkinsonism.
微管（MT）功能障碍在帕金森病中的作用正在显现。它是神经退行性变的原因还是后果仍不清楚。我们的目的是评估在 1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导的 C57Bl 小鼠实验性帕金森病中，MT 稳定性的改变是先于还是后于轴突运输损伤和神经突退化。MPTP 诱导纤维中线粒体分布改变、细胞骨架蛋白和 MT 稳定性的早期变化，呈时间和剂量依赖性。事实上，我们观察到神经元特异性βIII 微管蛋白和多巴胺能神经元中 deTyr 微管蛋白的含量显著增加。最后，我们表明，重复每日给予 MT 稳定剂埃坡霉素 D 可挽救 MT 缺陷，并减轻 MPTP 诱导的黑质纹状体变性。这些数据表明，MT 的改变是与多巴胺能神经元退化特异性相关的早期事件。MT 的药理学稳定可能是帕金森病治疗的可行策略。
