Prion proteins: a biological role beyond prion diseases.

The biological role of the scrapie isoform of prion protein (PrP(Sc)) as an infectious agent in numerous human and non-human disorders of the central nervous system is well established. In contrast, and despite decades of intensive research, the physiological function of the endogenous cellular form of the prion protein (PrP(C)) remains elusive. In mammals, the ubiquitous expression of PrP(C) suggests biological functions other than its pathological role in propagating the accumulation of its misfolded isotype. Other functions that have been attributed to PrP(C) include signal transduction, synaptic transmission and protection against cell death through the apoptotic pathway. More recently, immunoregulatory properties of PrP(C) have been reported. We review accumulating in vitro and in vivo evidence regarding physiological functions of PrP(C).