Brain proteins that mind metals: a neurodegenerative perspective

There are numerous neurodegenerative diseases but Alzheimer's disease and Parkinson's disease are the most common. In contrast, prion diseases are very rare but have sparked vast interest and study because of their potential threat. All three diseases have a common basis as they are linked to proteins that either aggregate or have break down products that aggregate. Even more strikingly, the three central proteins are metal binding proteins. Copper binds to both the prion protein and the amyloid precursor protein. Recently, alpha-synuclein has also been shown to bind copper. While study of the amyloid precursor protein (APP) and copper has not flourished since its discovery in the early 1990s and alpha-synuclein has only recently been a target for metallochemical investigation, the prion protein has been the centre of extensive research for the last decade. Therefore, recent insights into the metallochemistry of the prion protein are relevant to investigating APP and alpha-synuclein. This review considers what is known of the metallochemistry of all three proteins.