Brunden Kurt R, Lee Virginia M-Y, Smith Amos B, Trojanowski John Q, Ballatore Carlo
Center for Neurodegenerative Disease Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States.
Center for Neurodegenerative Disease Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States.
Neurobiol Dis. 2017 Sep;105:328-335. doi: 10.1016/j.nbd.2016.12.021. Epub 2016 Dec 22.
Many neurodegenerative diseases are characterized by deficiencies in neuronal axonal transport, a process in which cellular cargo is shuttled with the aid of molecular motors from the cell body to axonal termini and back along microtubules (MTs). Proper axonal transport is critical to the normal functioning of neurons, and impairments in this process could contribute to the neuronal damage and death that is characteristic of neurodegenerative disease. Although the causes of axonal transport abnormalities may vary among the various neurodegenerative conditions, in many cases it appears that the transport deficiencies result from a diminution of axonal MT stability. Here we review the evidence of MT abnormalities in a number of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and traumatic brain injury, and highlight the potential benefit of MT-stabilizing agents in improving axonal transport and nerve function in these diseases. Moreover, we discuss the challenges associated with the utilization of MT-stabilizing drugs as therapeutic candidates for neurodegenerative conditions.
许多神经退行性疾病的特征是神经元轴突运输缺陷，在这个过程中，细胞货物借助分子马达沿着微管从细胞体穿梭到轴突末端并返回。正常的轴突运输对神经元的正常功能至关重要，这一过程中的损伤可能导致神经退行性疾病所特有的神经元损伤和死亡。尽管轴突运输异常的原因在各种神经退行性疾病中可能有所不同，但在许多情况下，运输缺陷似乎是由于轴突微管稳定性降低所致。在这里，我们综述了多种神经退行性疾病（包括阿尔茨海默病、帕金森病、肌萎缩侧索硬化症和创伤性脑损伤）中微管异常的证据，并强调了微管稳定剂在改善这些疾病中的轴突运输和神经功能方面的潜在益处。此外，我们还讨论了将微管稳定药物用作神经退行性疾病治疗候选药物所面临的挑战。
