Cellular prion protein function in copper homeostasis and redox signalling at the synapse


Address correspondence and reprint requests to Jochen W. Herms, Institut für Neuropathologie, Ludwig-Maximilians-Universität, Marchioninistraße 17, D-81377 München, Germany. E-mail: Jochen.Herms@inp.med.uni-muenchen.de


The fundamental physiological function of native cellular prion (PrPC) remains unknown. Herein, the most salient observations as regards prion physiology are critically evaluated. These include: (i) the role of PrPC in copper homeostasis, particularly at the pre-synaptic membrane; (ii) involvement of PrPC in neuronal calcium disturbances; and (iii) the neuroprotective properties of PrPC in response to copper and oxidative stress. Ultimately, a tentative hypothesis of basic prion function is derived, namely that PrPC acts as a sensor for copper and/or free radical stimuli, thereby triggering intracellular calcium signals that finally translate into modulation of synaptic transmission and maintenance of neuronal integrity.