Copper, zinc and iron in neurodegenerative diseases (Alzheimer's, Parkinson's and prion diseases)

The basic role of metal ions including copper, zinc and iron in neurological pathologies is generally accepted. The relationship between the development of disease and particular metal ions is very complicated and complex. Thus, comprehension of metal homeostasis, details of transport and interactions with biomolecules is essential for understanding the normal and pathological processes occurring in the living system. Homeostasis of metal ions usually involves a huge set of proteins which regulate the proper metal biology. Disorder in metal homeostasis may result in serious pathologies including neurodegenerative diseases. Metal ions, especially copper, zinc and iron play very important roles in neurodegeneration having impact on both protein structure (misfolding) and oxidative stress. Metal ion binding to proteins involved in neurodegeneration is therefore an important factor for whole brain damage processes. All these aspects are discussed in the review.

► Critical aspects of metal ions involvement in neurodegenerative disorders are discussed. ► The thermodynamic aspects of key proteins interactions with copper, zinc and iron are reviewed. ► The hypothetical mechanisms of protein misfolding are presented. ► The interrelations of deregulation of metal ion homeostasis and oxidative stress are enlighten.