Metal ions in neurodegeneration

The role of cofactors, like transition metal ions, in folding, misfolding and aggregating proteins and peptides within cells and tissues is now well recognized [1]. Therefore, metal ions provide a tight linkage between neurodegeneration and aging or oxidative stress and inflammation, all events associated to metal ions dishomeostasis. Due to the low degree of structure in protein regions involved in such important interactions, experimental in vitro methods need complementary information provided by molecular models and high-performance computing infrastructures are providing an essential help in the field. As an example, three amyloid-beta peptides (involved in Alzheimer's disease) can be assembled by Zn ions (left), consistently with the high His-crowding around Zn revealed by X-ray absorption spectroscopy (right) [2]. In this contribution, the effects of Cu and Zn in the modulation of structural and chemical properties of the amyloid-beta peptide will be summarized [3].