Neurometals in the Pathogenesis of Prion Diseases.

Prion diseases are progressive and transmissive neurodegenerative diseases. The conformational conversion of normal cellular prion protein (PrP ^C ) into abnormal pathogenic prion protein (PrP ^Sc ) is critical for its infection and pathogenesis. PrP ^C possesses the ability to bind to various neurometals, including copper, zinc, iron, and manganese. Moreover, increasing evidence suggests that PrP ^C plays essential roles in the maintenance of homeostasis of these neurometals in the synapse. In addition, trace metals are critical determinants of the conformational change and toxicity of PrP ^C . Here, we review our studies and other new findings that inform the current understanding of the links between trace elements and physiological functions of PrP ^C and the neurotoxicity of PrP ^Sc .