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Figure 3. Hypothetical model of inflammation-mediated axonal transport impairment. TNF released by activated microglia during neuroinflammatory or neurodegenerative disease causes activation of JNK (JNK phosphorylated; pJNK), which subsequently acts on the conformation of the kinesin motor complexes and detaches kinesin from microtubule. Breakage of the kinesin-tubulin complex will lead to reversible cessation of the axonal transport and decrease of the mobile fraction of mitochondria and synaptic vesicle precursors moving along axons. Our data suggest that intact axonal transport is a sign of healthy neurons and that stress signaling over JNK acts on the motor transport possibly to reduce energy expenditure during inflammation.
