Florenzano Fulvio
Confocal Microscopy Unit, EBRI and S. Lucia Foundation, Via Fosso del Fiorano, 64/65-00143 Rome, Italy.
Int J Mol Sci. 2012;13(4):5195-5206. doi: 10.3390/ijms13045195. Epub 2012 Apr 24.
Axonal transport and neuronal survival depend critically on active transport and axon integrity both for supplying materials and communication to different domains of the cell body. All these actions are executed through cytoskeleton, transport and regulatory elements that appear to be disrupted in neurodegenerative diseases. Motor-driven transport both supplies and clears distal cellular portions with proteins and organelles. This transport is especially relevant in projection and motor neurons, which have long axons to reach the farthest nerve endings. Thus, any disturbance of axonal transport may have severe consequences for neuronal function and survival. A growing body of literature indicates the presence of alterations to the motor molecules machinery, not only in expression levels and phosphorylation, but also in their subcellular distribution within populations of neurons, which are selectively affected in the course of neurodegenerative diseases. The implications of this altered subcellular localization and how this affects axon survival and neuronal death still remain poorly understood, although several hypotheses have been suggested. Furthermore, cytoskeleton and transport element localization can be selectively disrupted in some disorders suggesting that specific loss of the axonal functionality could be a primary hallmark of the disorder. This can lead to axon degeneration and neuronal death either directly, through the functional absence of essential axonal proteins, or indirectly, through failures in communication among different cellular domains. This review compares the localization of cytoskeleton and transport elements in some neurodegenerative disorders to ask what aspects may be essential for axon survival and neuronal death.
轴突运输和神经元存活严重依赖于主动运输和轴突完整性，这两者对于向细胞体的不同区域供应物质和进行通信都至关重要。所有这些作用都是通过细胞骨架、运输和调节元件来执行的，而这些元件在神经退行性疾病中似乎会受到破坏。马达驱动的运输既为远端细胞部分提供蛋白质和细胞器，又清除这些物质。这种运输在投射神经元和运动神经元中尤为重要，因为它们有长长的轴突以到达最远的神经末梢。因此，轴突运输的任何干扰都可能对神经元功能和存活产生严重后果。越来越多的文献表明，运动分子机制存在改变，不仅在表达水平和磷酸化方面，而且在神经元群体中的亚细胞分布方面，这些在神经退行性疾病过程中会受到选择性影响。尽管已经提出了几种假说，但这种亚细胞定位改变的影响以及它如何影响轴突存活和神经元死亡仍然知之甚少。此外，在某些疾病中，细胞骨架和运输元件的定位可能会被选择性破坏，这表明轴突功能的特定丧失可能是该疾病的主要标志。这可能直接通过必需轴突蛋白的功能缺失，或间接通过不同细胞区域之间通信的失败导致轴突退化和神经元死亡。本综述比较了细胞骨架和运输元件在一些神经退行性疾病中的定位，以探讨哪些方面可能对轴突存活和神经元死亡至关重要。
