Iron crystals may play a role in neurodegenerative diseases

Nancy D. Lamontagne

Although iron is necessary for some cellular functions, it also can cause damage in certain forms. For example, iron deposits in the brain may contribute to neurodegenerative diseases such as Parkinson’s, Huntington’s and Alzheimer’s.

Optical microscopy has revealed that iron-loaded transferrin tends to aggregate. Images reprinted with permission from Angewandte Chemie.

The iron ions (Fe³⁺) present in the body always must be enclosed so that they do not cause damage. In blood plasma, iron is carried by the transport protein transferrin. An ion binds to the protein in a way that shields it from exposure to the surrounding environment, and it is only released once inside a cell. It is thought that a malfunction of transferrin may play a role in the iron deposits of neurodegenerative diseases. Thus, Peter J. Sadler at the University of Warwick in Coventry, UK, and Sandeep Verma of the Indian Institute of Technology in Kanpur decided to study human iron-loaded transferrin in more detail.

Atomic force microscopy of iron-loaded transferrin in solution revealed fibrous networks (left). The other images show magnified views of a fused fiber from the left image.

They did so by depositing iron-loaded human transferrin onto various surfaces under conditions that may be present in living organisms. Microscopy images taken with a variety of methods, including optical, atomic force and transmission electron microscopy, showed that transferrin tended to aggregate into long wormlike fibrils. The fibrils had a regular striped pattern, with the dark stripes containing something similar to rust. Within these fibrils, the iron ions were no longer properly enclosed and were arranged into nanocrystals whose structure seems to be very similar to that of the iron oxide mineral lepidocrocite. The investigation was reported in the March 7, 2008, issue of Angewandte Chemie International Edition.

The researchers think that, in some neurodegenerative diseases, iron deposits similar to the ones they observed may form in the brain. The iron crystals are highly reactive and could lead to the formation of toxic free radicals that attack and destroy nerve cells. If this can be verified in vivo, the information could be useful for developing drugs to prevent transferrin from aggregating.

Transmission electron microscopy images revealed banding in the fibrils. Within the bands, iron takes on a nanocrystalline structure.