Doppel: the prion's double.

Doppel (Dpl) is a PrP-like protein, coded by a gene named PRND, located near the PRNP (prion proten coding gene) locus. Human Dpl is a 179-amino acid protein showing approximately 25% sequence identity with the carboxyproximal two thirds of the human cellular prion protein (PrPC). A comparison of the structures of Dpl and PrP(C) reveals similarities in the secondary structure and topology. Apart from their structural similarities, the PrP and Dpl proteins seem to have different functions. The Prnd gene is expressed in mouse embryos; in adult mice its transcripts are present in heart, mammary gland, spleen, testes and, in contrast to Prnp, only at very low levels in the adult CNS. Moreover, the Dpl protein is not capable of enhancing the propagation of the pathological prion protein (PrP(Sc)). The Dpl protein has been identified as a regulator of acrosome function and male gametogenesis. The human PRND open reading frame has been shown to contain polymorphic codons, but research on a correlation between the PRND polymorphic sequences and neurodegenerative disorders carried out to date in different populations have shown contradictory results. Therefore, the role of the PRND gene in CJD and other diseases still remains unexplained.