Prion Protein: The Molecule of Many Forms and Faces

Cellular prion protein (PrP(C)) is a glycosylphosphatidylinositol (GPI)-anchored protein most abundantly found in the outer membrane of neurons. Due to structural characteristics (a flexible tail and structured core), PrP(C) interacts with a wide range of partners. Although PrP(C) has been proposed to be involved in many physiological functions, only peripheral nerve myelination homeostasis has been confirmed as a bona fide function thus far. PrP(C) misfolding causes prion diseases and PrP(C) has been shown to mediate beta-rich oligomer-induced neurotoxicity in Alzheimer's and Parkinson's disease as well as neuroprotection in ischemia. Upon proteolytic cleavage, PrP(C) is transformed into released and attached forms of PrP that can, depending on the contained structural characteristics of PrP(C), display protective or toxic properties. In this review, we will outline prion protein and prion protein fragment properties as well as overview their involvement with interacting partners and signal pathways in myelination, neuroprotection and neurodegenerative diseases.