Vickers James C, King Anna E, Woodhouse Adele, Kirkcaldie Matthew T, Staal Jerome A, McCormack Graeme H, Blizzard Catherine A, Musgrove Ruth E J, Mitew Stanislaw, Liu Yao, Chuckowree Jyoti A, Bibari Olivier, Dickson Tracey C
NeuroRepair Group and Wicking Dementia Research and Education Centre, Menzies Research Institute, University of Tasmania, Hobart, Tasmania, Australia.
Brain Res Bull. 2009 Oct 28;80(4-5):217-23. doi: 10.1016/j.brainresbull.2009.08.004. Epub 2009 Aug 13.
There has been growing interest in the axon as the initial focus of pathological change in a number of neurodegenerative diseases of the central nervous system. This review concentrates on three major neurodegenerative conditions--amyotrophic lateral sclerosis, multiple sclerosis and Alzheimer's disease--with emphasis on key cellular changes that may underlie early axonal dysfunction and pathology and, potentially, the degeneration of neurons. In particular, this review will address recent data that indicate that the main pathological stimuli for these conditions, though often not definitively determined, result in an initial perturbation of the axon and its cytoskeleton, which then results in slow neuronal degeneration and loss of connectivity. The identification of a degenerative process initiated in the axon may provide new therapeutic targets for early intervention to inhibit the grim outcomes related to the progression of these diseases.
在中枢神经系统的一些神经退行性疾病中，轴突作为病理变化的初始焦点已引起越来越多的关注。本综述集中于三种主要的神经退行性疾病——肌萎缩侧索硬化症、多发性硬化症和阿尔茨海默病——重点关注可能是早期轴突功能障碍和病理以及潜在的神经元变性基础的关键细胞变化。特别是，本综述将探讨最近的数据，这些数据表明，尽管这些疾病的主要病理刺激因素往往尚未明确确定，但它们会导致轴突及其细胞骨架的初始扰动，进而导致神经元缓慢变性和连接丧失。确定在轴突中启动的退行性过程可能为早期干预提供新的治疗靶点，以抑制与这些疾病进展相关的严峻后果。
