A transmembrane form of the prion protein in neurodegenerative disease.

@article{Hegde1998ATF,
  title={A transmembrane form of the prion protein in neurodegenerative disease.},
  author={Ramanujan S. Hegde and James A. Mastrianni and Michael R. Scott and Kathryn A. Defea and Patrick J. Tremblay and Marilyn Torchia and Stephen J. DeArmond and Stanley B. Prusiner and Vishwanath R. Lingappa},
  journal={Science},
  year={1998},
  volume={279 5352},
  pages={
          827-34
        }
}
At the endoplasmic reticulum membrane, the prion protein (PrP) can be synthesized in several topological forms. The role of these different forms was explored with transgenic mice expressing PrP mutations that alter the relative ratios of the topological forms. Expression of a particular transmembrane form (termed CtmPrP) produced neurodegenerative changes in mice similar to those of some genetic prion diseases. Brains from these mice contained CtmPrP but not PrPSc, the PrP isoform responsible… Expand
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TLDR
What is known about the cell biology of PrPC is reviewed, the understanding of which is crucial considering that trafficking of this molecule governs generation of PrPSc. Expand
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TLDR
The current evidence for such effects of single point mutations is discussed, indicating that PrP can be affected in many different ways, although questions remain about the mechanism by which mutations cause disease. Expand
THREE Cell Biology of Prion Protein
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Topics in prion cell biology
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  • Medicine, Biology
  • Current Opinion in Neurobiology
  • 1999
TLDR
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TLDR
Understanding the mechanism of conformational conversion of prion protein is essential for the biomedical research and the treatment of prions, and the characterization of cofactors interacting with prionprotein might provide new diagnostic and therapeutic strategies. Expand
Prion Protein Biogenesis: Implications for Neurodegeneration
TLDR
The studies lead to the hypothesis that CtmPrP is a transducer of signals for apoptotic neuronal cell death, and it is suggested that PrP is just one of a family of complex proteins that are regulated at the level of co-translational translocation, whose dysregulation results in disease. Expand
Cell Biology of Prion Protein.
TLDR
The latest findings on the fundamental aspects of prions biology are reviewed, from the PrPC biosynthesis, function, and structure up to its intracellular traffic and the possible roles of the different topological isoforms of the protein, as well as the GPI anchor, in the pathogenesis of the disease are analyzed. Expand
A transmembrane form of the prion protein contains an uncleaved signal peptide and is retained in the endoplasmic Reticulum.
TLDR
It is shown that a mutant form of PrP that is synthesized exclusively with the (Ctm)PrP topology is retained in the endoplasmic reticulum and is degraded by the proteasome, and it is demonstrated that the mutant contains an uncleaved, N-terminal signal peptide as well as a C-Terminal glycolipid anchor. Expand
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