Chapter 23: Manganese and Prion Disease

Prion diseases are a class of fatal neurodegenerative diseases caused by misfolding of the endogenous prion protein (PrP^C) induced by exposure to the pathogenic conformational isomer of PrP (PrP^Sc) or by heritable mutation of PrP^C. Although the exact role of the protein has yet to be determined, considerable evidence reveals prion protein to be a metalloprotein harboring divalent metal-binding sites for various cations such as copper, manganese, zinc, and nickel. Despite low-affinity binding to prion protein, when manganese interacts with prion, it can alter the development and transmission of prion disease. In this chapter, the role of metals in the pathogenesis of prion disease will be discussed. Particular emphasis will be placed on the link between manganese and PrP^C.