Figure 8. Model for oxidative stress linked to peroxisome trafficking.
In healthy axons an adequate microtubule network allows normal numbers of peroxisomes to travel at normal speeds in anterograde and retrograde directions (A: large circle). In SPAST-mutated axons the reduced microtubule network reduces the number of peroxisomes causing fewer peroxisomes to travel more slowly, with a larger effect on retrograde transport (B: large circle). In healthy neurons the peroxisome transport is enough to assure normal peroxisome distributions in cell body and distal axon and appropriate redox state (A: small circles). In SPAST-mutated neurons impaired peroxisome transport causes a build-up of peroxisomes at the distal end of the axon, with reduced peroxisome turnover at the cell body leading to oxidative stress (B: small circles).