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微管去稳定化导致帕金森病。

Microtubule Destabilization Paves the Way to Parkinson's Disease.

机构信息

Department Biosciences, Università degli Studi di Milano, Via Celoria 26, Milano, 20133, Italy.

Center of Excellence on Neurodegenerative Diseases, Università degli Studi di Milano, Milano, Italy.

出版信息

Mol Neurobiol. 2017 Nov;54(9):6762-6774. doi: 10.1007/s12035-016-0188-5. Epub 2016 Oct 18.

Abstract

Microtubules are dynamic structures normally associated to the cell division, during which they form the mitotic spindle, as well as to the initial phases of specification and polarization of various cell types, including neurons. Although microtubules could have a role in the death of many cells and tissues, the microtubule-based degenerative mechanisms have been poorly investigated; nevertheless, during the last two decades, many clues have been accumulated suggesting the importance of the microtubule system during neurodegeneration. Thus, the aim of this review is to analyse how the changes of the microtubule cytoskeleton, in terms of organization and dynamics, as well as the failure of the microtubule-dependent neuronal processes, as axonal transport, may play a pivotal role in the chain of events leading to Parkinson's disease. Last but not least, since disease-modifying or neuroprotective strategies are a clinical priority in Parkinson's disease, we will also present the hints about the concrete possibility of a microtubule-targeted therapy, which would have the potentiality to block the running degenerative events and to prompt the regeneration of the lost tissues.

摘要

微管是与细胞分裂相关的动态结构,在此过程中它们形成有丝分裂纺锤体,以及各种细胞类型(包括神经元)的特化和极化的初始阶段。尽管微管可能在许多细胞和组织的死亡中发挥作用,但基于微管的退行性机制尚未得到充分研究;然而,在过去的二十年中,已经积累了许多线索,表明微管系统在神经退行性变中的重要性。因此,本综述的目的是分析微管细胞骨架的变化,包括组织和动力学,以及微管依赖性神经元过程(如轴突运输)的失败,如何在导致帕金森病的一系列事件中发挥关键作用。最后但同样重要的是,由于疾病修饰或神经保护策略是帕金森病的临床重点,我们还将介绍关于微管靶向治疗的具体可能性的线索,该治疗具有阻断进行性退行性事件和促使丢失组织再生的潜力。

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