Axonal Transport and Cytoskeletal Incorporation of Neurofilaments

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IBN 98-09878 SHEA. "Neurons" (the cells of the brain) transmit electrical and chemical signals that allow us to think, feel and move. Neurons connect to each other by long extensions of their bodies termed "axons". These axons function essentially like telephone wires, allowing neurons to transmit their signals to each other. Neurons are unlike other cells in the body in that they are never replaced. Once a neuron dies, its functions are therefore lost forever. Accordingly, excessive loss of neurons, or disconnection of their axons, can lead to human disorders such as Lou Gerhig's Disease, Alzheimer's Disease or mental retardation. Importantly, the axons are supported internally by a scaffold comprised of many proteins. These proteins interconnect like building blocks, a form a skeleton (the "cytoskeleton") within the axon itself. This cytoskeleton maintains the shape of the axon like girders can hold up a building. Unlike the static girders of a building, however, the cytoskeleton of the axon must continually be repaired and maintained with new building blocks. This process places a considerable burden on neurons. Our studies address how neurons manage to maintain this scaffold for a person's lifetime, and will identify particular aspects of this process that are prone to errors that may lead to disconnection of neurons.