Within the body, iron is present in the form of iron ions with a threefold positive charge (Fe3+) and must always be well "wrapped" to prevent it from reacting with proteins and causing damage. In blood plasma, iron is carried in the "pockets" of the iron transport protein transferrin. It only gets unwrapped once it is inside special cellular organelles.
But things can go wrong in this system, as Sadler and his colleagues have now proved. The researchers deposited iron-loaded human transferrin onto various surfaces under conditions that emulate those in living organisms. By using microscopy and electron microscopy, the researchers showed that the proteins aggregate into long wormlike fibrils. These "worms" have a regular striped pattern; the narrow dark stripes contain something similar to rust. "Within the fibrils, the iron ions are no longer properly enclosed;" explains Sadler, "instead, they aggregate into periodically arranged nanocrystals whose structure seems to be very similar to the iron oxide mineral lepidocrocite".
The researchers suspect that in certain forms of neurodegenerative disease, iron deposits may form in a similar fashion in the brain. Such iron crystals are highly reactive and could lead to the formation of toxic free radicals, which attack and destroy nerve cells. If this assumption can be verified in vivo, agents that hinder the aggregation of transferrin may be the foundation for a new family of drugs.