Eira Jessica, Silva Catarina Santos, Sousa Mónica Mendes, Liz Márcia Almeida
Neurodegeneration Group, IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, 4200 Porto, Portugal; Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200 Porto, Portugal.
Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200 Porto, Portugal; Nerve Regeneration Group, IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, 4200 Porto, Portugal.
Prog Neurobiol. 2016 Jun;141:61-82. doi: 10.1016/j.pneurobio.2016.04.007. Epub 2016 Apr 16.
Cytoskeleton defects, including alterations in microtubule stability, in axonal transport as well as in actin dynamics, have been characterized in several unrelated neurodegenerative conditions. These observations suggest that defects of cytoskeleton organization may be a common feature contributing to neurodegeneration. In line with this hypothesis, drugs targeting the cytoskeleton are currently being tested in animal models and in human clinical trials, showing promising effects. Drugs that modulate microtubule stability, inhibitors of posttranslational modifications of cytoskeletal components, specifically compounds affecting the levels of tubulin acetylation, and compounds targeting signaling molecules which regulate cytoskeleton dynamics, constitute the mostly addressed therapeutic interventions aiming at preventing cytoskeleton damage in neurodegenerative disorders. In this review, we will discuss in a critical perspective the current knowledge on cytoskeleton damage pathways as well as therapeutic strategies designed to revert cytoskeleton-related defects mainly focusing on the following neurodegenerative disorders: Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Amyotrophic Lateral Sclerosis and Charcot-Marie-Tooth Disease.
细胞骨架缺陷，包括微管稳定性、轴突运输以及肌动蛋白动力学的改变，已在几种不相关的神经退行性疾病中得到表征。这些观察结果表明，细胞骨架组织缺陷可能是导致神经退行性变的一个共同特征。与此假设一致，目前正在动物模型和人体临床试验中测试针对细胞骨架的药物，显示出有前景的效果。调节微管稳定性的药物、细胞骨架成分翻译后修饰的抑制剂，特别是影响微管蛋白乙酰化水平的化合物，以及靶向调节细胞骨架动力学的信号分子的化合物，构成了旨在预防神经退行性疾病中细胞骨架损伤的最主要治疗干预措施。在这篇综述中，我们将以批判性的视角讨论关于细胞骨架损伤途径的当前知识，以及旨在恢复细胞骨架相关缺陷的治疗策略，主要聚焦于以下神经退行性疾病：阿尔茨海默病、帕金森病、亨廷顿病、肌萎缩侧索硬化症和夏科-马里-图斯病。
