Small is not beautiful:: antagonizing functions for the prion protein PrPC and its homologue Dpl

conformational variant of the normal prion protein PrPc is believed to be identical to PrPsc, the agent that causes prion diseases. Recently, a novel protein, named Doppel (DpI), was identified that shares significant biochemical and structural homology with PrPc. In specific strains of PrPc-deficient mouse lines, DpI is overexpressed and causes a neurological disease. DpI neurotoxicity is counteracted and prevented by PrPc, but the mechanism of antagonistic PrPc-DpI interaction remains elusive. In contrast to its homologue PrPc, initial studies suggest that Dpl is dispensable for prion disease progression and for the generation of PrPsc. Although we are only beginning to understand its function, the discovery of DpI has already provided some answers to long-standing questions and is transforming our understanding of prion biology.