Axonal transport and amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis is an adult-onset neurodegenerative disease affecting large motor neurons in the brain and spinal cord. Transport of molecules and organelles is a fundamental process in all cells, including neurons. Transport is central to neuronal development, survival, intracellular signaling and trafficking. Microtubules are polarized within axons, such that their plus-ends are directed towards the synapse, and their minus-ends towards the cell body. Dynein is thought to be the major retrograde transport motor in neurons. Transport of cargoes by the molecular motor proteins described above proceeds at fast rates. The immobilized motors ‘walk’ along the microtubules, displacing them. The microtubule movement can be imaged using fluorescence microscopy, and information about the velocity of the motor determined. The most straightforward assays rely on phase contrast or differential interference contrast microscopy. The label is incorporated into newly synthesized proteins, which are transported into the axons of the optic or sciatic nerve.