Angewandte Chemie International Edition 2008, 47, 2221–2231
Rusty Worms in the Brain
Nanomineralization of iron: Does the iron transporter transferrin play a role in neurodegenerative diseases?
Contact: Peter J. Sadler, University of Warwick, Coventry (UK)
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Periodic Iron Nanomineralization in Human Serum Transferrin Fibrils
Iron is vital to human life; for example, it is a component of
hemoglobin, the substance that makes our blood red and supplies our
cells with oxygen. However, iron can also cause heavy damage; it is
thought that iron deposits in the brain contribute to certain forms of
neurodegenerative diseases such as Parkinsons’s, Huntington’
s, and Alzheimer’s. A malfunction of the blood transporter transferrin
may be to blame. A team led by Peter J. Sadler at the University of
Warwick (Coventry, UK) and Sandeep Verma of the Indian Institute of
Technology (Kanpur, India) has now been able to show that transferrin
can clump together to form wormlike fibrils. As reported in the journal
Angewandte Chemie, this process releases rustlike iron particles.
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
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 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.