FIGURE 4 | Axonal transport is abnormal in ALS.

The motors for anterograde and retrograde fast axonal transport are the kinesins and dynactin complex proteins, respectively; microtubules provide the tracks for these motors. Vesicles for transport are sorted and loaded onto transport motors both in the cell body and the distal nerve terminal. The former are transported not only into the axon but also into dendrites. Those in the distal nerve terminal permit uptake and axosomatic movement of substances such as trophic proteins. Mutations in dynactin (humans), dynein (mice) and three different forms of kinesin all provoke motor neuron degeneration. Perturbation of neurofilaments through mutations and changes in phosphorylation and the physical structure of the axon could also adversely affect axonal transport. In transgenic mouse models, mutant superoxide dismutase 1 (SOD1) impairs anterograde axonal transport. ER, endoplasmic reticulum.

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