The prion protein family: Diversity, rivalry, and dysfunction

The prion gene family currently consists of three members: Prnp which encodes PrPC, the precursor to prion disease associated isoforms such as PrPSc; Prnd which encodes Doppel, a testis-specific protein involved in the male reproductive system; and Sprn which encodes the newest PrP-like protein, Shadoo, which is expressed in the CNS. Although the identification of numerous candidate binding partners for PrPC has hinted at possible cellular roles, molecular interpretations of PrPC activity remain obscure and no widely-accepted view as to PrPC function has emerged. Nonetheless, studies into the functional interrelationships of prion proteins have revealed an interesting phenomenon: Doppel is neurotoxic to cerebellar cells in a manner which can be blocked by either PrPC or Shadoo. Further examination of this paradigm may help to shed light on two prominent unanswered questions in prion biology: the functional role of PrPC and the neurotoxic pathways initiated by PrPSc in prion disease.