| First Author | Christensen HM | Year | 2010 |
| Journal | Am J Pathol | Volume | 176 |
| Issue | 6 | Pages | 2695-706 |
| PubMed ID | 20472884 | Mgi Jnum | J:161315 |
| Mgi Id | MGI:4457982 | Doi | 10.2353/ajpath.2010.091007 |
| Citation | Christensen HM, et al. (2010) A highly toxic cellular prion protein induces a novel, nonapoptotic form of neuronal death. Am J Pathol 176(6):2695-706 |
| abstractText | Several different deletions within the N-terminal tail of the prion protein (PrP) induce massive neuronal death when expressed in transgenic mice. This toxicity is dose-dependently suppressed by coexpression of full-length PrP, suggesting that it results from subversion of a normal physiological activity of cellular PrP. We performed a combined biochemical and morphological analysis of Tg(DeltaCR) mice, which express PrP carrying a 21-aa deletion (residues 105-125) within a highly conserved region of the protein. Death of cerebellar granule neurons in Tg(DeltaCR) mice is not accompanied by activation of either caspase-3 or caspase-8 or by increased levels of the autophagy marker, LC3-II. In electron micrographs, degenerating granule neurons displayed a unique morphology characterized by heterogeneous condensation of the nuclear matrix without formation of discrete chromatin masses typical of neuronal apoptosis. Our data demonstrate that perturbations in PrP functional activity induce a novel, nonapoptotic, nonautophagic form of neuronal death whose morphological features are reminiscent of those associated with excitotoxic stress. |
