| First Author | Guillot-Sestier MV | Year | 2009 |
| Journal | J Biol Chem | Volume | 284 |
| Issue | 51 | Pages | 35973-86 |
| PubMed ID | 19850936 | Mgi Jnum | J:158196 |
| Mgi Id | MGI:4438270 | Doi | 10.1074/jbc.M109.051086 |
| Citation | Guillot-Sestier MV, et al. (2009) The alpha-secretase-derived N-terminal product of cellular prion, N1, displays neuroprotective function in vitro and in vivo. J Biol Chem 284(51):35973-86 |
| abstractText | Cellular prion protein (PrP(c)) undergoes a disintegrin-mediated physiological cleavage, generating a soluble amino-terminal fragment (N1), the function of which remained unknown. Recombinant N1 inhibits staurosporine-induced caspase-3 activation by modulating p53 transcription and activity, whereas the PrP(c)-derived pathological fragment (N2) remains biologically inert. Furthermore, N1 protects retinal ganglion cells from hypoxia-induced apoptosis, reduces the number of terminal deoxynucleotidyltransferase-mediated biotinylated UTP nick end labeling-positive and p53-immunoreactive neurons in a pressure-induced ischemia model of the rat retina and triggers a partial recovery of b-waves but not a-waves of rat electroretinograms. Our work is the first demonstration that the alpha-secretase-derived PrP(c) fragment N1, but not N2, displays in vivo and in vitro neuroprotective function by modulating p53 pathway. It further demonstrates that distinct N-terminal cleavage products of PrP(c) harbor different biological activities underlying the various phenotypes linking PrP(c) to cell survival. |
