Fig. 1: Transmission electron microscope images of of human transferrin fibres showing periodic dark spots of iron.

Researchers in India and the UK have discovered that a protein in the bloodstream called transferrin can aggregate into long fibres. These tranferrin fibres carry tiny iron mineral particles that might be the cause of brain diseases such as Parkinson’s, Huntingdon’s or Alzheimer’s.

Iron ions in the bloodstream can form insoluble particles in a process known as biomineralization. These iron particles can be extremely useful, for example they act as magnetic navigational aids for certain bacteria. However excess amounts of iron minerals have also been linked to degenerative brain diseases.

The transferrin protein acts to carefully store, transport and release iron in the body. Each transferrin molecule is composed of two lobes, each of which is shaped like a small cleft with a hinged lid to hold the iron ions until they are needed.

In the new study, Sandeep Verma at the Indian Institute of Technology in Kanpur, Peter Sadler at the University of Warwick and co-workers1 looked at human transferrin deposited on a glass slide, and found that the molecules aggregated into long intertwined fibres. Closer examination with a transmission electron microscope revealed dark spots at periodic spacing along the length of each fibre. The dark spots were studied with X-ray diffraction, which showed that they were particles of biomineralized iron.

The researchers offer several explanations as to how this biomineralization takes place. Firstly, the transferrin molecules are believed to straighten out when they form fibres, opening up their lobes to release iron ions. The iron may then mineralize in cavities left empty when carbonate bound to iron in the protein is released as carbon dioxide.

A further possibility is that iron accumulates at the growing tip of the transferrin fibres until it becomes saturated and forms minerals. Repeated cycles of this process could produce the periodic spots of iron minerals.

The researchers hope to investigate whether transferrin forms fibres in real human tissues. If so, the fibres may be linked to the abnormal accumulation of iron in the brain that causes diseases. New drugs could be designed to prevent transferrin from aggregating into fibres.