Axonal transport and neurodegenerative disease
Neurons are highly dependent on an efficient and finely tuned transport system for the delivery of organelles as well as structural and signalling proteins into the axons and for transporting neurotrophic factors from the axon termini to the cell body. The major components of this transport system are a group of specialized motor proteins plus the cytoskeletal networks of microtubules and actin filaments. Motor proteins use these networks as intracellular tracks for transporting their cargos.
Defects in axonal transport have been implicated in the pathogenesis of several neurodegenerative diseases including motor neuron disease. Mutations in the molecular motors dynein and kinesins and several proteins associated with the membranes of intracellular vesicles that undergo transport cause motor neuron degeneration in humans and mice. My laboratory uses a number of mouse models and motor neurons differentiated from induced pluripotent stem (iPS) cells to elucidate the molecular mechanisms of the role of defective axonal transport in the pathogenesis of motor neuron disease.