From cell protection to death: may Ca2+ signals explain the chameleonic attributes of the mammalian prion protein?
It is now accepted that a conformational change of the cellular prion protein (PrP(C)) generates the prion, the infectious agent responsible for lethal neurodegenerative disorders, named transmissible spongiform encephalopathies, or prion diseases. The mechanisms of prion-associated neurodegeneration are still obscure, as is the cell role of PrP(C), although increasing evidence attributes to PrP(C) important functions in cell survival. Such a behavioral dichotomy thus enables the prion protein to switch from a benign role under normal conditions, to the execution of neurons during disease. By reviewing data from models of prion disease and PrP(C)-null paradigms, which suggest a relation between the prion protein and Ca(2+) homeostasis, here we discuss the possibility that Ca(2+) is the factor behind the enigma of the pathophysiology of PrP(C). Ca(2+) features in almost all processes of cell signaling, and may thus tell us much about a protein that pivots between health and disease.
Sorgato
M Catia
MC
Department of Biological Chemistry and CNR Institute of Neuroscience, University of Padova, Viale G. Colombo 3, 35131 Padova, Italy. catia.sorgato@unipd.it
Bertoli
Alessandro
A
D000818:Animals; D020013:Calcium Signaling; D019610:Cytoprotection; D006801:Humans; D018621:PrPC Proteins / Q000378:metabolism / Q000502:physiology*; D017096:Prion Diseases / Q000378:metabolism*
D018621:PrPC Proteins