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The cytoskeleton of neurons is the nanoscale matrix along which organelles, proteins, mRNAs, or signaling complexes are guided to their final destinations inside the cell. Nanotechnology and molecular biology have enabled precision study of these biomolecular machines, in some cases down to the level of single molecules. Motor, linker, and adaptor proteins are essential to the transport process – the three main motors being kinesin, dynein, and myosin, each of which give rise to families of related motor proteins. Neurons are unique in that they possess two distinct transport systems: one in the axon and the other in the somatodendritic compartment. Microtubules are the main tracks for transport in the axon shaft, with neurofilaments (also concentrated within axons) stabilizing the microtubule network. Synaptic vesicles, containing biosynthetic enzymes that are responsible for manufacturing and releasing neurotransmitters, are routinely transported down along axonal microtubules towards actin–rich axon terminals. Endosomes incorporating neurotrophins typically travel in the reverse direction, from axon terminal to the cell body. These transport processes have been tracked with quantum dot nanoparticles attached to single motor proteins or individual cargo molecules. Microtubules also fill the somatodendritic compartments of neurons where they are pivotal to the transport of neurotransmitter receptor subunits and mRNAs from the cell body to postsynaptic sites, in particular to spines – the postsynaptic specializations enriched with actin filaments. Levels of synaptic activity affect the transport of neurotransmitter receptors and mRNA, and permanent changes in synaptic strength partly depend on transport to postsynaptic sites. Alterations in axonal and dendritic transport underlie neuronal responses to injury, regeneration and morphogenesis, as well as learning and memory. Modifications of transport tracks may constitute a subcellular memory mechanism by which the altered intraneuronal connectivity contributes to the memory trace. Elucidation of this mechanism of memory will come with a greater understanding of the biophysics of transport and motor protein mechanics. Biophysical models detailing the nanoscale mechanisms of cellular transport have already increased our understanding of how biological motors operate mechanistically, providing fundamental guiding principles for nanotechnological advancements. Potential nanotechnologies expected to result from biophysical studies of biological transport include bioengineered motors and biomimetic nanocarrier devices, both promising to be useful in biomedicine or as analytical devices. Cytoskeletal and motor proteins, or hybrid designs including these proteins, stand to contribute to a wide variety of potential nanostructured products.

RNA transport in dendrites, and subsequent local translation in postsynaptic microdomains, have increasingly been recognized as potentially powerful tools for neurons in long-term modulations of individual synapses (see reviews by Steward 1997; Kuhl and Skehel 1998; Tiedge et al. 1999). While analogous mechanisms have also been reported to be employed by other cell types (reviewed by Bassell et al. 1999), neurons face a particular challenge in that thousands of synapses per dendritic arborization (many of which at considerable distances from the soma) have to be regulated in an independent and input-specific manner. It now appears plausible that such regulation is achieved by two mechanisms: (1) targeted delivery of specific proteins to dendritic sites of demand, and (2) dendritic transport of select RNAs, followed by local postsynaptic translation when and where needed.

Neuroaxonal Dystrophy in Man: Character and Natural History.- Neuropathological Conditions Related to Neuroaxonal Dystrophy.- Infantile Neuroaxonal Dystrophy or Seitelberger's Disease: II. Peripheral Nerve Involvement. Electron Microscopy Study in one Case.- How Long Can Degenerating Axons in the Central Nervous System Produce Reactive Changes? An Electron Microscopic Investigation.- Fine Structural Changes of Neurites in Alzheimer's Disease.- Mitochondrial Changes in Axonal Dystrophy Produced by Vitamin E Difficiency.- Permeability of Blood Vessels and Connective Tissue Sheaths in the Peripheral Nervous System to Exogenous Proteins.- Changes in Axonal Flow During Regeneration of Mammalian Motor Nerves.- Nuclear, Cytoplasmic and Axoplasmic RNA in Experimental Neuroaxonal Dystrophy.- The Dependence of Fast Transport in Mammalien Nerve Fibers on Metabolism.- Slow and Rapid Transport of Protein to Nerve Endings in Mouse Brain.- Transport of S-100 Protein in Mammalian Nerve Fibers and Transneuronal Signals.- Dynamic Condition of Protein in Axons and Axon Terminales.- Effect of Nerve Section on Protein Metabolism of Ganglion Cells and Preganglionic Nerve Endings.- Some Observations on the Experimental Production of Acute Neuroaxonal and Synaptosomal Dystrophy.- Independence of the Rapid Axonal Transport of Protein from the Flow of Free Amino Acids.- Acetylcholinesterase in Mammalian Peripheral Nerves and Characteristics of its Migration.- Role of Slow Axonal Transport in Nerve Regeneration.- Axoplasmic Streaming and Proteins in the Retino-Tectal Neurons of the Pigeon.- Different Modes of Substance Flow in the Optic Tract.- A Symmetrical Double-Label Method for Studying the Rapid Axonal Transport of Radioactivity from Labelled d-Glucosamine in the Gold Fish Visual System.- Single Cell Isotope Injection Technique, a Tool for Studying Axonal and Dendritic Transport.- Neuronal Organelles in Neuroplasmic ("Axonal") Flow, I. Mitochondria.- Neuronal Organelles in Neuroplasmic ("Axonal") Flow, II. Neurotubules.- Axonal Transport of Proteins in the Optic Nerve and Tract of the Rabbit.- Changes in Microtubules and Neurofilaments in Constricted, Hypoplastic Nerve Fibers.- Effects of Vinblastine and Colchicine on Monoamine Containing Neurons of the Rat, with Special Regard to the Axoplasmic Transport of Amine Granules.- The Importance of Axoplasmic Transport of Amine Granules for the Functions of Adrenergic Neurons.- Axonal Transport of Proteins in the Hypothalamo-Neurohypophysial System of the Rat.- Axonal Transport in the Goldfish Visual System.