Prion and other amyloid-forming diseases represent a group of neurodegenerative disorders that affect both animals and humans. The role of metal ions, especially copper and zinc is studied intensively in connection with these diseases. Their involvement in protein misfolding and aggregation and their role in creation of reactive oxygen species have been shown. Recent data also show that metal ions not only bind the proteins with high affinity, but also modify their biochemical properties, making them important players in prion-related diseases. In particular, the level of zinc ions is tightly regulated by several mechanisms, including transporter proteins and the low molecular mass thiol-rich metallothioneins. From four metallothionein isoforms, metallothionein-3, a unique brain-specific metalloprotein, plays a crucial role only in this regulation. This review critically evaluates the involvement of metallothioneins in prion- and amyloid-related diseases in connection with the relationship between metallothionein isoforms and metal ion regulation of their homeostasis.

Central European Institute of Technology Brno University of Technology Technicka Brno Czech Republic

Department of Chemistry and Biochemistry Mendel University in Brno Zemedelska 1 Brno Czech Republic

Department of Physiology Faculty of Medicine Masaryk University Kamenice Brno Czech Republic

Faculdade de Ciências Universidade de Lisboa Biosystems and Integrative Sciences Institute and Department of Chemistry and Biochemistry Universidade de Lisboa Campo Grande Lisboa Portugal

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