Study of Whether Neurofilaments Undergo Axonal Transport as Cargo of Microtubules

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Like the entire body, the brain is composed of cells. Neurons, the "thinking" cells of the brain are unique in that they connect to each other by long, extensions which received and transmit electrical signals. The transmitting connections ("axons") are quite long, and are maintained by an internal skeleton (the "cytoskeleton") that is comprised of an unique interconnected network of fibers. These fibers themselves are assembled from repetitive subunits that are manufactured in the neuron's body and transported into the axon by a process called "axonal transport". It remains unclear how the major fibers ("neurofilaments" NFs and "microtubules") are organized and how they undergo axonal transport. What is clear, however, is that the proper development of axons (and therefore that of the entire nervous system) is dependent upon the proper transport and accumulation of neurofilaments and microtubules within developing axons. Furthermore, failure to maintain these fibers during later life can lead to axonal atrophy and the progressive neuronal death associated with aging and Alzheimer's disease. In other cell types, microtubules are known to slide past one another by means of associated motor-like proteins that "walk" one microtubule along another one. Similar proteins are used to move membrane-enclosed packets of material along microtubules into the axon. Dr. Shea and colleagues hypothesize that neurofilaments make their way out into the axon by traveling as cargo of microtubules, perhaps via similar associated motor proteins. They will test this hypothesis by introducing drugs that cripple several distinct aspects of microtubule assembly and axonal transport. If their hypothesis is correct, Dr. Shea and his colleagues anticipate that these drugs will also cause axonal transport of neurofilaments to cease.