| First Author | Yoshikawa D | Year | 2008 |
| Journal | J Biol Chem | Volume | 283 |
| Issue | 35 | Pages | 24202-11 |
| PubMed ID | 18562311 | Mgi Jnum | J:140370 |
| Mgi Id | MGI:3813424 | Doi | 10.1074/jbc.M804212200 |
| Citation | Yoshikawa D, et al. (2008) Dominant-negative effects of the N-terminal half of prion protein on neurotoxicity of prion protein-like protein/doppel in mice. J Biol Chem 283(35):24202-11 |
| abstractText | Prion protein-like protein/doppel is neurotoxic, causing ataxia and Purkinje cell degeneration in mice, whereas prion protein antagonizes doppel-induced neurodegeneration. Doppel is homologous to the C-terminal half of prion protein but lacks the amino acid sequences corresponding to the N-terminal half of prion protein. We show here that transgenic mice expressing a fusion protein consisting of the N-terminal half, corresponding to residues 1-124, of prion protein and doppel in neurons failed to develop any neurological signs for up to 730 days in a background devoid of prion protein. In addition, the fusion protein prolonged the onset of ataxia in mice expressing exogenous doppel. These results suggested that the N-terminal part of prion protein has a neuroprotective potential acting both cis and trans on doppel. We also show that prion protein lacking the pre-octapeptide repeat (Delta25-50) or octapeptide repeat (Delta51-90) region alone could not impair the antagonistic function against doppel. |
