Metals are involved in both of the neurodegenerative processes in prion diseases: “loss of normal protective functions of PrPC” and “gain of toxic functions of PrPSc.” According to the “loss-of-function neurodegenerative pathway,” several neurological dysfunctions, including the death of Purkinje neurons in the cerebellum, synaptic dysfunction, demyelination, depressive-like behavior, and memory loss in knockout mice of PrPC. This evidence concerns the gene PRNP and prion disease.