Involvement of Trace Elements in the Pathogenesis of Prion Diseases

Title:Involvement of Trace Elements in the Pathogenesis of Prion Diseases

Volume: 15 Issue: 11

Author(s): Dai Mizuno, Hironari Koyama, Susumu Ohkawara, Yutaka Sadakane and Masahiro Kawahara

Affiliation:

Keywords: Amyloid, combinaconformational disease, calcium homeostasis, synapse.

Abstract: Prion diseases are progressive neurodegenerative diseases that are associated with conformational changes that convert normal cellular prion protein (PrP^C) into an abnormal pathogenic prion protein (PrP^Sc). It is widely recognized that prion diseases are forms of transmissible amyloidosis and are considered to be protein-misfolding diseases (conformational diseases), a category that also includes Alzheimer’s disease. Trace elements play crucial roles in the conformational change affecting PrP^C, and increasing evidence suggests that PrP^C is a metal-binding protein that is involved in the homeostasis of Cu, Zn, and Fe. In this article, we review the current understanding of links between trace elements and the conformational change to PrP^Sc, based on our studies using synthetic prion peptides, as well as other new findings. We also focus on PrP^Sc-induced disruption of Ca homeostasis as a molecular mechanism for neurodegeneration in prion diseases. Possible roles of carnosine (ß-alanyl histidine) as a candidate neuroprotective substance use in prion diseases are also discussed.

Cite this article as:

Mizuno Dai, Koyama Hironari, Ohkawara Susumu, Sadakane Yutaka and Kawahara Masahiro, Involvement of Trace Elements in the Pathogenesis of Prion Diseases, Current Pharmaceutical Biotechnology 2014; 15 (11) . https://dx.doi.org/10.2174/1389201015666141103020625