Department of Molecular and Experimental Medicine, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California 92037; email:
Annu Rev Biophys. 2014;43:141-69. doi: 10.1146/annurev-biophys-051013-022746.
Axonal transport is indispensable for the distribution of vesicles, organelles, messenger RNAs (mRNAs), and signaling molecules along the axon. This process is mediated by kinesins and dyneins, molecular motors that bind to cargoes and translocate on microtubule tracks. Tight modulation of motor protein activity is necessary, but little is known about the molecules and mechanisms that regulate transport. Moreover, evidence suggests that transport impairments contribute to the initiation or progression of neurodegenerative diseases, or both, but the mechanisms by which motor activity is affected in disease are unclear. In this review, we discuss some of the physical and biophysical properties that influence motor regulation in healthy neurons. We further discuss the evidence for the role of transport in neurodegeneration, highlighting two pathways that may contribute to transport impairment-dependent disease: genetic mutations or variation, and protein aggregation. Understanding how and when transport parameters change in disease will help delineate molecular mechanisms of neurodegeneration.
轴突运输对于囊泡、细胞器、信使 RNA（mRNA）和信号分子沿着轴突的分布是必不可少的。这个过程是由驱动蛋白和动力蛋白介导的，它们与货物结合并在微管轨道上移动。需要对马达蛋白活性进行严格的调节，但对于调节运输的分子和机制知之甚少。此外，有证据表明，运输障碍会导致神经退行性疾病的发生或进展，或者两者兼而有之，但在疾病中马达活性受到影响的机制尚不清楚。在这篇综述中，我们讨论了一些影响健康神经元中马达调节的物理和生物物理特性。我们进一步讨论了运输在神经退行性变中的作用的证据，强调了可能导致运输障碍相关疾病的两种途径：遗传突变或变异和蛋白质聚集。了解运输参数在疾病中是如何以及何时发生变化的，将有助于阐明神经退行性变的分子机制。
