The parkinsonism producing neurotoxin MPP+ affects microtubule dynamics by acting as a destabilising factor
The parkinsonism producing neurotoxin MPP+ affects microtubule dynamics by acting as a destabilising factor
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DOI：
10.1016/j.febslet.2005.07.058
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发表时间：
2005-08-29
期刊：
影响因子：
3.5
通讯作者：
Maci, R
中科院分区：
文献类型：
--
作者：
Cappelletti, G;Surrey, T;Maci, R
微管系统功能障碍正在成为许多神经退行性疾病的促成因素。为了寻找微管细胞骨架在帕金森病 (PD) 神经元变性中所起的潜在作用，我们研究了帕金森病产生的神经毒素 1-甲基-4-苯基吡啶鎓 (MPP+) 对微管动力学的影响。我们发现它作为一种强大的灾难促进剂，导致由纯化的微管蛋白组装的微管的平均长度减少。我们还发现它减少了纯化中心体成核的微管数量。最后，结合测定表明神经毒素以接近化学计量的方式与微管晶格中的微管蛋白特异性结合。本文提供了第一个证据，表明微管的动态不稳定性特别受到 MPP+ 的影响，并表明它可能在 PD 潜在的神经元细胞死亡中发挥作用。 (c) 2005 年欧洲生化学会联合会。由 Elsevier B.V. 出版。保留所有权利。
Dysfunction of the microtubule system is emerging as a contributing factor in a number of neurodegenerative diseases. Looking for the potential role played by the microtubule cytoskeleton in neuron degeneration underlying Parkinson's disease (PD), we investigate the influence of the parkinsonism producing neurotoxin 1-methyl-4-phenylpyridinium (MPP+) on microtubule dynamics. We find that it acts as a strong catastrophe promoter causing a decrease of the average length of microtubules assembled from purified tubulin. We also find that it reduces the number of microtubules nucleated from purified centrosomes. Finally, binding assays demonstrate that the neurotoxin binds specifically to tubulin in the microtubule lattice in a close to stoichiometric manner. This paper provides the first evidence that dynamic instability of microtubules is specifically affected by MPP+ and suggests that it could play a role in neuronal cell death underlying PD. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.