The therapeutic opportunities and pitfalls of using iron ion chelators to treat neurodegenerative diseases

There is considerable evidence that iron accumulation in the affected brain regions plays a role in the pathology of neurodegenerative diseases, probably because of the ability of iron ions to promote oxidative damage to important biomolecules, such as DNA, RNA, proteins and lipids (leading to lipid peroxidation). Yet recent clinical trials of iron ion-chelating agents in human neurodegenerative diseases have given unimpressive results, in several cases making the diseases worse. In using iron chelators, it is important to remember the basics of their redox chemistry, which could explain their lack of therapeutic effects. This issue is explored here, and the potential of iron ion chelation in the treatment of neurodegeneration is critically evaluated.