PMID: 17703189

 

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Title : The CNS glycoprotein Shadoo has PrP ( C )-like protective properties and displays reduced levels in prion infections

Abstract :

1. The cellular prion protein , PrP ( C ), is neuroprotective in a number of settings and in particular prevents cerebellar degeneration mediated by CNS-expressed Doppel or internally deleted PrP ('Delta PrP ')
2. This paradigm has facilitated mapping of activity determinants in PrP ( C ) and implicated a cryptic PrP ( C )-like protein , 'pi'
3. Shadoo ( Sho ) is a hypothetical GPI-anchored protein encoded by the Sprn gene, exhibiting homology and domain organization similar to the N-terminus of PrP
4. Here we demonstrate Sprn expression and Sho protein in the adult CNS
5. Sho expression overlaps PrP ( C ), but is low in cerebellar granular neurons (CGNs) containing PrP ( C ) and high in PrP ( C )-deficient dendritic processes
6. In Prnp (0/0) CGNs, Sho transgenes were PrP ( C )-like in their ability to counteract neurotoxic effects of either Doppel or Delta PrP
7. Additionally, prion-infected mice exhibit a dramatic reduction in endogenous Sho protein
8. Sho is a candidate for pi, and since it engenders a PrP ( C )-like neuroprotective activity, compromised neuroprotective activity resulting from reduced levels may exacerbate damage in prion infections
9. Sho may prove useful in deciphering several unresolved facets of prion biology