Washington, March 6 : Researchers at the Indian Institute of Technology Kanpur, India, and the University of Warwick, UK, have found that the mechanism that transports iron safely through our blood stream can, in some circumstances, malfunction due to long worm-like "fibrils" banded by lines of iron rust.
Researchers at the Indian Institute of Technology Kanpur, India, and the University of Warwick, UK, have found that the mechanism that transports iron safely through our blood stream can, in some circumstances, malfunction due to long worm-like "fibrils" banded by lines of iron rust.
Peter J. Sadler at the University of Warwick (Coventry, UK) and Sandeep Verma of IIT Kanpur said that this process could provide the first insight into how iron gets deposited in the brain to cause some forms of Parkinson's, Alzheimer's and Huntington's diseases.
Human blood relies on a protein called transferrin to safely transport iron through the bloodstream to points were it can be usefully and safely used in the body. In most other circumstances exposed iron contains many dangers for human cells. When deposited in such a state in the brain it can play a role in neurodegenerative diseases such as Parkinson's, Huntington's and Alzheimer's
Transferrin takes up iron out of bloodstream and transports it by a method that combines it with carbonate to bind to two sites on the surface of the transferrin protein. It then curls around the iron and seals it in, almost like a Venus flytrap plant, to prevent it from interacting with anything else until it reaches where it is needed and can safely be used.
But things can go wrong in this system, as Sadler and his colleagues have now proven.
The researchers deposited iron-loaded human transferrin onto various surfaces under conditions that imitate 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; instead, they aggregate into periodically arranged nanocrystals whose structure seems to be very similar to the iron oxide mineral lepidocrocite," Sadler said.
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.
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